An autosomal recessive cutaneous porphyria that is due to a deficiency of UROPORPHYRINOGEN DECARBOXYLASE in both the LIVER and the BONE MARROW. Similar to PORPHYRIA CUTANEA TARDA, this disorder is caused by defects in the fifth enzyme in the 8-enzyme biosynthetic pathway of HEME, but is a homozygous enzyme deficiency with less than 10% of the normal enzyme activity. Cutaneous lesions are severe and mutilating.
An enzyme that catalyzes the decarboxylation of UROPORPHYRINOGEN III to coproporphyrinogen III by the conversion of four acetate groups to four methyl groups. It is the fifth enzyme in the 8-enzyme biosynthetic pathway of HEME. Several forms of cutaneous PORPHYRIAS are results of this enzyme deficiency as in PORPHYRIA CUTANEA TARDA; and HEPATOERYTHROPOIETIC PORPHYRIA.
A diverse group of metabolic diseases characterized by errors in the biosynthetic pathway of HEME in the LIVER, the BONE MARROW, or both. They are classified by the deficiency of specific enzymes, the tissue site of enzyme defect, or the clinical features that include neurological (acute) or cutaneous (skin lesions). Porphyrias can be hereditary or acquired as a result of toxicity to the hepatic or erythropoietic marrow tissues.
A group of metabolic diseases due to deficiency of one of a number of LIVER enzymes in the biosynthetic pathway of HEME. They are characterized by the accumulation and increased excretion of PORPHYRINS or its precursors. Clinical features include neurological symptoms (PORPHYRIA, ACUTE INTERMITTENT), cutaneous lesions due to photosensitivity (PORPHYRIA CUTANEA TARDA), or both (HEREDITARY COPROPORPHYRIA). Hepatic porphyrias can be hereditary or acquired as a result of toxicity to the hepatic tissues.
An autosomal dominant porphyria that is due to a deficiency of HYDROXYMETHYLBILANE SYNTHASE in the LIVER, the third enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features are recurrent and life-threatening neurologic disturbances, ABDOMINAL PAIN, and elevated level of AMINOLEVULINIC ACID and PORPHOBILINOGEN in the urine.
An autosomal recessive porphyria that is due to a deficiency of UROPORPHYRINOGEN III SYNTHASE in the BONE MARROW; also known as congenital erythropoietic porphyria. This disease is characterized by SPLENOMEGALY; ANEMIA; photosensitivity; cutaneous lesions; accumulation of hydroxymethylbilane; and increased excretion of UROPORPHYRINS and COPROPORPHYRINS.
An autosomal dominant porphyria that is due to a deficiency of protoporphyrinogen oxidase (EC 1.3.3.4) in the LIVER, the seventh enzyme in the 8-enzyme biosynthetic pathway of HEME. Clinical features include both neurological symptoms and cutaneous lesions. Patients excrete increased levels of porphyrin precursors, COPROPORPHYRINS and protoporphyrinogen.
An autosomal dominant or acquired porphyria due to a deficiency of UROPORPHYRINOGEN DECARBOXYLASE in the LIVER. It is characterized by photosensitivity and cutaneous lesions with little or no neurologic symptoms. Type I is the acquired form and is strongly associated with liver diseases and hepatic toxicities caused by alcohol or estrogenic steroids. Type II is the familial form.
An enzyme that catalyzes the tetrapolymerization of the monopyrrole PORPHOBILINOGEN into the hydroxymethylbilane preuroporphyrinogen (UROPORPHYRINOGENS) in several discrete steps. It is the third enzyme in the 8-enzyme biosynthetic pathway of HEME. In humans, deficiency in this enzyme encoded by HMBS (or PBGD) gene results in a form of neurological porphyria (PORPHYRIA, ACUTE INTERMITTENT). This enzyme was formerly listed as EC 4.3.1.8
Porphobilinogen is a porphyrin precursor, specifically the organic compound intermediate in the biosynthesis of heme and chlorophyll, formed by the condensation of two pyrrole molecules in the liver and other tissues.
A membrane-bound flavoenzyme that catalyzes the oxygen-dependent aromatization of protoporphyrinogen IX (Protogen) to protoporphyrin IX (Proto IX). It is the last enzyme of the common branch of the HEME and CHLOROPHYLL pathways in plants, and is the molecular target of diphenyl ether-type herbicides. VARIEGATE PORPHYRIA is an autosomal dominant disorder associated with deficiency of protoporphyrinogen oxidase.
A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin.
An enzyme that catalyzes the cyclization of hydroxymethylbilane to yield UROPORPHYRINOGEN III and water. It is the fourth enzyme in the 8-enzyme biosynthetic pathway of HEME, and is encoded by UROS gene. Mutations of UROS gene result in CONGENITAL ERYTHROPOIETIC PORPHYRIA.

Inheritance in erythropoietic protoporphyria: a common wild-type ferrochelatase allelic variant with low expression accounts for clinical manifestation. (1/24)

Erythropoietic protoporphyria (EPP) is a rare autosomal dominant disorder of heme biosynthesis characterized by partial decrease in ferrochelatase (FECH; EC 4.99.1.1) activity with protoporphyrin overproduction and consequent painful skin photosensitivity and rarely liver disease. EPP is normally inherited in an autosomal dominant pattern with low clinical penetrance; the many different mutations that have been identified are restricted to one FECH allele, with the other one being free of any mutations. However, clinical manifestations of dominant EPP cannot be simply a matter of FECH haploinsufficiency, because patients have enzyme levels that are lower than the expected 50%. From RNA analysis in one family with dominant EPP, we recently suggested that clinical expression required coinheritance of a normal FECH allele with low expression and a mutant FECH allele. We now show that (1) coinheritance of a FECH gene defect and a wild-type low-expressed allele is generally involved in the clinical expression of EPP; (2) the low-expressed allelic variant was strongly associated with a partial 5' haplotype [-251G IVS1-23T IVS2microsatA9] that may be ancestral and was present in an estimated 10% of a control group of Caucasian origin; and (3) haplotyping allows the absolute risk of developing the disease to be predicted for those inheriting FECH EPP mutations. EPP may thus be considered as an inherited disorder that does not strictly follow recessive or dominant rules. It may represent a model for phenotype modulation by mild variation in expression of the wild-type allele in autosomal dominant diseases.  (+info)

Correction of uroporphyrinogen decarboxylase deficiency (hepatoerythropoietic porphyria) in Epstein-Barr virus-transformed B-cell lines by retrovirus-mediated gene transfer: fluorescence-based selection of transduced cells. (2/24)

Hepatoerythropoietic porphyria (HEP) is an inherited metabolic disorder characterized by the accumulation of porphyrins resulting from a deficiency in uroporphyrinogen decarboxylase (UROD). This autosomal recessive disorder is severe, starting early in infancy with no specific treatment. Gene therapy would represent a great therapeutic improvement. Because hematopoietic cells are the target for somatic gene therapy in this porphyria, Epstein-Barr virus-transformed B-cell lines from patients with HEP provide a model system for the disease. Thus, retrovirus-mediated expression of UROD was used to restore enzymatic activity in B-cell lines from 3 HEP patients. The potential of gene therapy for the metabolic correction of the disease was demonstrated by a reduction of porphyrin accumulation to the normal level in deficient transduced cells. Mixed culture experiments demonstrated that there is no metabolic cross-correction of deficient cells by normal cells. However, the observation of cellular expansion in vitro and in vivo in immunodeficient mice suggested that genetically corrected cells have a competitive advantage. Finally, to facilitate future human gene therapy trials, we have developed a selection system based on the expression of the therapeutic gene. Genetically corrected cells are easily separated from deficient ones by the absence of fluorescence when illuminated under UV light.  (+info)

Haplotype analysis of families with erythropoietic protoporphyria and novel mutations of the ferrochelatase gene. (3/24)

Ferrochelatase, the enzyme that catalyzes the terminal step in the heme biosynthetic pathway, is the site of the defect in the human inherited disease erythropoietic protoporphyria. Molecular genetic studies have shown that the majority of erythropoietic protoporphyria cases are transmitted in dominant fashion and that mutations underlying erythropoietic protoporphyria are heterogeneous. We performed haplotype analysis of American families that shared recurrent ferrochelatase gene mutations yet had forbearers from several European countries. This was to gain insight into whether these mutations represent mutational hotspots at the ferrochelatase gene, or propagation of ancestral alleles bearing the mutations. Two recurrent mutations were found to occur on distinctive chromosome 18 haplotypes, consistent with being hotspot mutations. On the other hand, we found three sets of two unrelated families that shared the same haplotypes bearing these mutations, which could reflect geographic dispersion of ancestral mutant alleles. In addition, we report novel mutations associated with erythropoietic protoporphyria: g(+ 1)-->t transversion of the exon 4 donor site, g(+ 1)-->a transition of the exon 6 donor site, and t(+ 2)-->a substitution at the exon 9 donor site; these mutations are predicted to cause splicing defects of the associated exons. We also identified a g(+ 5)-->a transition of the exon 1 donor site in four unrelated families with erythropoietic protoporphyria, and a G(- 1)-->A substitution at the exon 9 donor site in an additional family. The probability that these sequence changes are normal polymorphisms was virtually excluded (p < 0.0001) by their absence in 120 ferrochelatase alleles from 30 normal subjects and 30 individuals with manifested erythropoietic protoporphyria with or without a known mutation.  (+info)

Mutations in the iron-sulfur cluster ligands of the human ferrochelatase lead to erythropoietic protoporphyria. (4/24)

Ferrochelatase (FECH; EC 4.99.1.1) catalyzes the terminal step of the heme biosynthetic pathway. Defects in the human FECH gene may lead to erythropoietic protoporphyria (EPP), a rare inherited disorder characterized by diminished FECH activity with protoporphyrin overproduction and subsequent skin photosensitivity and in rare cases liver failure. Inheritance of EPP appeared to be autosomal dominant with possible modulation by low expression of the wild-type FECH allele. Animal FECHs have been demonstrated to be [2Fe-2S] cluster-containing proteins. Although enzymatic activity and stability of the protein appear to be dependent on the presence of the [2Fe-2S] cluster, the physiologic role of the iron-sulfur center remains to be unequivocally established. Three of the 4 [2Fe-2S] cluster-coordinating cysteines (ie, C403, C406, and C411 in the human enzyme) are located within the C-terminal domain. In this study 5 new mutations are identified in patients with EPP. Three of the point mutations, in 3 patients, resulted in FECH variants with 2 of the [2Fe-2S] cluster cysteines substituted with tyrosine, serine, and glycine (ie, C406Y, C406S, and C411G) and with undetectable enzymatic activity. Further, one of the patients exhibited a triple point mutation (T(1224)-->A, C(1225)-->T, and T(1231)-->G) leading to the N408K/P409S/C411G variant. This finding is entirely novel and has not been reported in EPP. The mutations of the codons for 2 of the [2Fe-2S] cluster ligands in patients with EPP supports the importance of the iron-sulfur center for the proper functioning of mammalian FECH and, in at least humans, its absence has a direct clinical impact. (Blood. 2000;96:1545-1549)  (+info)

Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria. (5/24)

Exposure to light precipitates the symptoms of several genetic disorders that affect both skin and internal organs. It is presumed that damage to non-cutaneous organs is initiated indirectly by light, but this is difficult to study in mammals. Zebrafish have an essentially transparent periderm for the first days of development. In a previous large-scale genetic screen we isolated a mutation, dracula (drc), which manifested as a light-dependent lysis of red blood cells [1]. We report here that protoporphyrin IX accumulates in the mutant embryos, suggesting a deficiency in the activity of ferrochelatase, the terminal enzyme in the pathway for heme biosynthesis. We find that homozygous drc(m248) mutant embryos have a G-->T transversion at a splice donor site in the ferrochelatase gene, creating a premature stop codon. The mutant phenotype, which shows light-dependent hemolysis and liver disease, is similar to that seen in humans with erythropoietic protoporphyria, a disorder of ferrochelatase.  (+info)

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells. (6/24)

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FACS from deficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hematopoiesis. This selection system represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.  (+info)

Gene therapy of a mouse model of protoporphyria with a self-inactivating erythroid-specific lentiviral vector without preselection. (7/24)

Successful treatment of blood disorders by gene therapy has several complications, one of which is the frequent lack of selective advantage of genetically corrected cells. Erythropoietic protoporphyria (EPP), caused by a ferrochelatase deficiency, is a good model of hematological genetic disorders with a lack of spontaneous in vivo selection. This disease is characterized by accumulation of protoporphyrin in red blood cells, bone marrow, and other organs, resulting in severe skin photosensitivity. Here we develop a self-inactivating lentiviral vector containing human ferrochelatase cDNA driven by the human ankyrin-1/beta-globin HS-40 chimeric erythroid promoter/enhancer. We collected bone marrow cells from EPP male donor mice for lentiviral transduction and injected them into lethally irradiated female EPP recipient mice. We observed a high transduction efficiency of hematopoietic stem cells resulting in effective gene therapy of primary and secondary recipient EPP mice without any selectable system. Skin photosensitivity was corrected for all secondary engrafted mice and was associated with specific ferrochelatase expression in the erythroid lineage. An erythroid-specific expression was sufficient to reverse most of the clinical and biological manifestations of the disease. This improvement in the efficiency of gene transfer with lentiviruses may contribute to the development of successful clinical protocols for erythropoietic diseases.  (+info)

Haplotype analysis in determination of the heredity of erythropoietic protoporphyria among Swiss families. (8/24)

Defects in the human ferrochelatase gene lead to the hereditary disorder of erythropoietic protoporphyria. The clinical expression of this autosomal dominant disorder requires an allelic combination of a disabled mutant allele and a low-expressed nonmutant allele. Unlike most other erythropoietic protoporphyria populations, mutations identified among Swiss erythropoietic protoporphyria families to date have been relatively homogeneous. In this study, genotype analysis was conducted in seven Swiss erythropoietic protoporphyria families, three carrying mutation Q59X, two carrying mutation insT213, and two carrying mutation delTACAG(580-584). Three different haplotypes of five known intragenic single nucleotide polymorphisms, namely -251 A/G, IVS1-23C/T, 798 G/C, 921 A/G, and 1520C/T, were identified. Each haplotype was shared by families carrying an identical mutation in the ferrochelatase gene indicating a single mutation event for each of the three mutations. These mutations have been present in the Swiss erythropoietic protoporphyria population for a relatively long time as no common haplotypes of microsatellite markers flanking the ferrochelatase gene were found, except of two conserved regions, telomeric of the insT213 allele and centromeric of the delTACAG(580-584)allele, each with a size > 3 cM. Among the nonmutant ferrochelatase alleles, patients from six erythropoietic protoporphyria families shared a common haplotype [-251G; IVS1-23T] of the first two single nucleotide polymorphisms. An exception was the haplotype [-251 A; IVS1-23C] identified in the index patient of one erythropoietic protoporphyria family. These results supported the recent findings that the low expressed allele is tightly linked to a haplotype [-251G; IVS1-23T] of two intragenic single nucleotide polymorphisms in the ferrochelatase gene.  (+info)

Hepatoerythropoietic porphyria (HEP) is a rare inherited metabolic disorder that affects the production of heme, a component in hemoglobin. It is a subtype of porphyria known as "erythropoietic porphyria," which primarily affects the bone marrow and erythroid cells.

In HEP, there are deficiencies in the activity of two enzymes involved in heme biosynthesis: uroporphyrinogen III synthase (UROS) and coproporphyrinogen oxidase (CPOX). This double enzyme deficiency leads to the accumulation of porphyrin precursors, particularly uroporphyrinogen I and coproporphyrinogen I, in erythrocytes, plasma, and tissues.

The main clinical manifestations of HEP include severe cutaneous photosensitivity, blistering, scarring, and hypertrichosis (excessive hair growth) on sun-exposed areas. Other features may include hemolytic anemia, splenomegaly, and liver dysfunction. The condition typically presents in infancy or early childhood, and it can be associated with significant morbidity and mortality if not properly managed.

Diagnosis of HEP is based on the detection of elevated levels of porphyrin precursors in plasma, erythrocytes, and stool, as well as genetic testing to confirm mutations in the UROS and CPOX genes. Treatment involves avoidance of sunlight exposure, use of sun-protective measures, and management of anemia with blood transfusions or other therapies. In some cases, hematopoietic stem cell transplantation may be considered as a curative treatment option.

Uroporphyrinogen decarboxylase is a vital enzyme in the biosynthetic pathway of heme, which is a crucial component of hemoglobin in red blood cells. This enzyme is responsible for catalyzing the decarboxylation of uroporphyrinogen III, a colorless porphyrinogen, to produce coproporphyrinogen III, a brownish-red porphyrinogen.

The reaction involves the sequential removal of four carboxyl groups from the four acetic acid side chains of uroporphyrinogen III, resulting in the formation of coproporphyrinogen III. This enzyme's activity is critical for the normal biosynthesis of heme, and any defects or deficiencies in its function can lead to various porphyrias, a group of metabolic disorders characterized by the accumulation of porphyrins and their precursors in the body.

The gene responsible for encoding uroporphyrinogen decarboxylase is UROD, located on chromosome 1p34.1. Mutations in this gene can lead to a deficiency in the enzyme's activity, causing an autosomal recessive disorder known as congenital erythropoietic porphyria (CEP), also referred to as Günther's disease. This condition is characterized by severe photosensitivity, hemolytic anemia, and scarring or thickening of the skin.

Porphyrias are a group of rare genetic disorders that affect the production of heme, a component in hemoglobin that carries oxygen in the blood. The diseases are caused by mutations in the genes involved in the production of heme, leading to the buildup of porphyrins or their precursors in the body. These substances can be toxic and can cause various symptoms depending on the specific type of porphyria. Symptoms may include abdominal pain, neurological problems, and skin issues. Porphyrias are typically divided into two categories: acute porphyrias, which affect the nervous system, and cutaneous porphyrias, which primarily affect the skin.

Hepatic porphyrias are a group of rare genetic disorders that affect the production of heme in the liver. Heme is a crucial component of hemoglobin, the protein in red blood cells that carries oxygen throughout the body. In hepatic porphyrias, there is a buildup of porphyrins or porphyrin precursors, which are toxic and can cause a variety of symptoms.

The four types of hepatic porphyrias are:

1. Acute Intermittent Porphyria (AIP): This is the most common type of hepatic porphyria. It is characterized by attacks of abdominal pain, nausea, vomiting, constipation, and neurological symptoms such as muscle weakness, seizures, and mental changes.
2. Variegate Porphyria (VP): This type of porphyria is more common in South Africa but can occur worldwide. It is characterized by skin symptoms such as blistering and scarring after exposure to sunlight, as well as acute attacks similar to those seen in AIP.
3. Hereditary Coproporphyria (HCP): This type of porphyria is similar to VP, but the symptoms are usually less severe. It can cause both skin symptoms and acute attacks.
4. ALA Dehydratase Deficiency Porphyria (ADDP): This is the rarest type of hepatic porphyria. It is characterized by severe neurological symptoms and is often diagnosed in infancy or early childhood.

The diagnosis of hepatic porphyrias typically involves measuring the levels of porphyrins and their precursors in the urine, blood, or stool during an attack or between attacks. Treatment may include avoiding trigger factors such as certain medications, alcohol, and smoking, as well as providing supportive care during acute attacks. In some cases, medication to reduce porphyrin production or prevent attacks may be necessary.

Acute Intermittent Porphyria (AIP) is a rare inherited metabolic disorder that affects the production of heme, a component in hemoglobin. This condition is part of a group of disorders known as the porphyrias, which are caused by genetic mutations that result in enzyme deficiencies needed to produce heme.

In AIP, specifically, there is a deficiency in the enzyme porphobilinogen deaminase (PBGD). This leads to the buildup of porphyrin precursors, particularly porphobilinogen and delta-aminolevulinic acid (ALA), in the body. These substances are toxic and can cause acute attacks when they accumulate in high concentrations.

Acute attacks are characterized by severe abdominal pain, nausea, vomiting, constipation or diarrhea, muscle weakness, seizures, and mental changes such as confusion, hallucinations, or anxiety. These symptoms can be triggered by certain factors like drugs, alcohol, hormonal changes, infections, or stress.

It is essential to differentiate AIP from other medical conditions that may present with similar symptoms, as the treatment strategies differ significantly. Diagnosis typically involves measuring porphyrin precursors in urine, especially during an acute attack, and can be confirmed by genetic testing for the PBGD gene mutation.

Treatment of AIP primarily focuses on managing acute attacks with intravenous heme preparations, which help to reduce the production of toxic porphyrin precursors. In addition, providing supportive care such as hydration, pain management, and addressing any triggers or complications is crucial. Long-term management includes avoiding identified triggers, monitoring for early signs of acute attacks, and implementing a low-purine diet in some cases.

Erythropoietic Porphyria (EP) is a rare inherited disorder of the heme biosynthesis pathway, specifically caused by a deficiency of the enzyme uroporphyrinogen III synthase. This results in the accumulation of porphyrin precursors, particularly uroporphyrin I and coproporphyrin I, in erythrocytes (red blood cells), bone marrow, and other tissues. The accumulation of these porphyrins leads to photosensitivity, hemolysis, and iron overload.

The symptoms of EP typically appear in childhood or early adulthood and include severe skin fragility and blistering, particularly on sun-exposed areas, which can result in scarring, disfigurement, and increased susceptibility to infection. Other features may include anemia due to hemolysis, iron overload, and splenomegaly (enlarged spleen).

The diagnosis of EP is based on clinical symptoms, laboratory tests measuring porphyrin levels in blood and urine, and genetic testing to confirm the presence of pathogenic variants in the UROS gene. Treatment for EP includes avoidance of sunlight exposure, use of sun-protective measures, and management of anemia with blood transfusions or erythropoietin injections. In some cases, bone marrow transplantation may be considered as a curative treatment option.

Variegate Porphyria (VP) is a rare inherited metabolic disorder that affects the production of heme, a component in hemoglobin. It is one of the types of porphyrias, which are caused by genetic mutations that result in deficiencies of enzymes needed to synthesize heme.

In variegate porphyria, the deficient enzyme is protoporphyrinogen oxidase (PPOX). This leads to the accumulation of porphyrins and their precursors, particularly coproporphyrin III and protoporphyrin, in the body. These substances can cause neurological symptoms when they are excreted in urine and exposed to light.

Variegate porphyria is characterized by both cutaneous (skin) and neurovisceral (neurological) manifestations. Cutaneous symptoms include skin sensitivity to sunlight, blistering, scarring, and fragility. Neurovisceral symptoms can include abdominal pain, nausea, vomiting, constipation, muscle weakness, seizures, and mental changes such as anxiety, hallucinations, or confusion.

The severity of variegate porphyria can vary widely between individuals, even among family members who carry the same genetic mutation. Symptoms may be triggered by certain medications, hormonal changes, alcohol consumption, infections, or other factors that increase heme synthesis. Diagnosis typically involves measuring porphyrin levels in blood and urine, as well as genetic testing for the PPOX gene mutation. Treatment usually focuses on managing symptoms, avoiding triggers, and providing supportive care during acute attacks.

Porphyria Cutanea Tarda (PCT) is a type of porphyria, a group of rare genetic disorders that affect the production of heme, a component in hemoglobin. PCT is primarily an acquired disorder, although it can have a hereditary component as well.

In PCT, there is a dysfunction in the enzyme uroporphyrinogen decarboxylase (UROD), which leads to the accumulation of porphyrins and porphyrin precursors in the skin. This buildup causes the characteristic symptoms of PCT, which include:

* Blisters, particularly on sun-exposed areas such as the hands and face
* Fragile, thin skin that tears easily
* Scarring
* Hypertrichosis (abnormal hair growth)
* Changes in skin color, including redness, increased pigmentation, or loss of pigment

PCT is typically triggered by factors such as alcohol consumption, estrogen use, hepatitis C infection, and exposure to certain chemicals. Treatment often involves addressing these triggers, along with the use of phlebotomy (removal of blood) or low-dose hydroxychloroquine to reduce porphyrin levels in the body.

It's important to note that PCT is a complex disorder and its diagnosis and management should be done by healthcare professionals with experience in managing porphyrias.

Hydroxymethylbilane Synthase (HMBS) is an enzyme that plays a crucial role in the metabolic pathway known as heme biosynthesis. Heme is an essential component of various proteins, including hemoglobin, which is responsible for oxygen transport in the blood.

The HMBS enzyme catalyzes the conversion of aminolevulinic acid (ALA) and glycine into a linear tetrapyrrole intermediate called hydroxymethylbilane. This reaction is the third step in the heme biosynthesis pathway, and it takes place in the mitochondria of cells.

Deficiencies in HMBS can lead to a rare genetic disorder called acute intermittent porphyria (AIP), which is characterized by neurovisceral attacks and neurological symptoms such as abdominal pain, vomiting, hypertension, tachycardia, and mental disturbances.

Porphobilinogen (PBG) is a bioactive compound that plays a crucial role in the biosynthesis pathway of heme, which is an essential component of hemoglobin and other hemoproteins. It is a porphyrin precursor and is synthesized from aminolevulinic acid (ALA) by the enzyme ALA dehydratase in the second step of heme biosynthesis.

In medical terms, abnormal accumulation or increased levels of PBG in the body can indicate an underlying disorder in heme biosynthesis, such as acute intermittent porphyria (AIP), variegate porphyria (VP), or hereditary coproporphyria (HCP). These disorders are known as porphyrias and are characterized by the buildup of porphyrin precursors in various tissues, leading to neurological and gastrointestinal symptoms.

Therefore, measuring PBG levels in urine or blood can help diagnose and monitor these conditions.

Protoporphyrinogen Oxidase (PPO) is a mitochondrial enzyme that plays a crucial role in the heme biosynthesis pathway. It catalyzes the oxidation of protoporphyrinogen IX to protporphyrin IX, which is the penultimate step in the production of heme. This enzyme is the target of certain herbicides, such as those containing the active ingredient diphenyl ether, and genetic deficiencies in PPO can lead to a rare genetic disorder called Protoporphyria.

Porphyrins are complex organic compounds that contain four pyrrole rings joined together by methine bridges (=CH-). They play a crucial role in the biochemistry of many organisms, as they form the core structure of various heme proteins and other metalloproteins. Some examples of these proteins include hemoglobin, myoglobin, cytochromes, and catalases, which are involved in essential processes such as oxygen transport, electron transfer, and oxidative metabolism.

In the human body, porphyrins are synthesized through a series of enzymatic reactions known as the heme biosynthesis pathway. Disruptions in this pathway can lead to an accumulation of porphyrins or their precursors, resulting in various medical conditions called porphyrias. These disorders can manifest as neurological symptoms, skin lesions, and gastrointestinal issues, depending on the specific type of porphyria and the site of enzyme deficiency.

It is important to note that while porphyrins are essential for life, their accumulation in excessive amounts or at inappropriate locations can result in pathological conditions. Therefore, understanding the regulation and function of porphyrin metabolism is crucial for diagnosing and managing porphyrias and other related disorders.

Uroporphyrinogen III Synthase is a crucial enzyme in the biosynthetic pathway of heme and chlorophyll. This enzyme, specifically classified under EC 4.2.1.75, catalyzes the conversion of coproporphyrinogen III to protoporphyrinogen IX, which is a key step in the synthesis of heme.

The reaction it facilitates is:

Coproporphyrinogen III + reduced ferredoxin → Protoporphyrinogen IX + oxidized ferredoxin + CO2

Deficiency or malfunctioning of this enzyme can lead to a rare genetic disorder known as "congenital erythropoietic porphyria" (CEP), also known as Günther's disease, which is characterized by severe photosensitivity and related symptoms.

ISBN 978-0-7216-2921-6. "hepatoerythropoietic porphyria" at Dorland's Medical Dictionary Hepatoerythropoietic porphyria at NLM ... Hepatoerythropoietic porphyria is a very rare form of hepatic porphyria caused by a disorder in both genes which code ... In classifications which define PCT type 1 as "sporadic" and PCT type 2 as "familial", hepatoerythropoietic porphyria is more ... February 2007). "Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP)". ...
... of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic porphyria and overt familial porphyria ... 1991). "Identification of a new mutation responsible for hepatoerythropoietic porphyria". Eur. J. Clin. Invest. 21 (2): 225-9. ... 1994). "Molecular defects of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria". J. Invest. ... 1998). "A zebrafish model for hepatoerythropoietic porphyria". Nat. Genet. 20 (3): 239-43. doi:10.1038/3041. PMID 9806541. ...
Hepatoerythropoietic porphyria List of cutaneous conditions Miyata T, Oda O, Inagi R, et al. (September 1993). "beta 2- ...
HMBS Porphyria, congenital erythropoietic; 263700; UROS Porphyria, hepatoerythropoietic; 176100; UROD Prader-Willi syndrome; ... SART3 Porphyria cutanea tarda; 176100; UROD Porphyria variegata; 176200; PPOX Porphyria, acute hepatic; 612740; ALAD Porphyria ... acute intermittent; 176000; HMBS Porphyria, acute intermittent, nonerythroid variant; 176000; ...
The most severe disease is seen in CEP and a rare variant of PCT known as hepatoerythropoietic porphyria (HEP); symptoms ... Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, ... "About Porphyria: Safety database". Porphyria Drug Safety Database. American Porphyria Foundation. Archived from the original on ... The non-acute porphyrias are X-linked dominant protoporphyria (XLDPP), congenital erythropoietic porphyria (CEP), porphyria ...
Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda, although it can also be ... Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often ... "Porphyria Cutanea Tarda (PCT)". 2020-01-12. "Porphyrin Tests". 7 May 2020. Jackson, A. H.; Ferramola, A. M.; Sancovich, H. A.; ... Porphyria Cutanea Tarda at eMedicine Held, H. (2009). "Effect of Alcohol on the Heme and Porphyrin Synthesis Interaction with ...
... intermittent porphyria Porphyria cutanea tarda and Hepatoerythropoietic porphyria Hereditary coproporphyria Variegate porphyria ... Hepatic porphyrias is a form of porphyria in which toxic porphyrin molecules build up in the liver. Hepatic porphyrias can ... Porphyrias,+Hepatic at the U.S. National Library of Medicine Medical Subject Headings (MeSH) www.drugs-porphyria.com www. ... Erythropoietic porphyria Givosiran "OMIM - PORPHYRIA, CONGENITAL ERYTHROPOIETIC". Retrieved 2008-12-04. ...
Hemodialysis-associated amyloidosis Hepatoerythropoietic porphyria Hereditary coproporphyria Hereditary gelsolin amyloidosis ... mixed hepatic porphyria, mixed porphyria, South African genetic porphyria, South African porphyria) Verruciform xanthoma Waxy ... Alkaptonuria Aminolevulinic acid dehydratase deficiency porphyria (Doss porphyria, plumboporphyria) B-mannosidase deficiency ... Porphyria cutanea tarda Primary cutaneous amyloidosis Primary systemic amyloidosis Prolidase deficiency Pseudoporphyria ( ...
... or hep may refer to: Hepatitis, a medical condition of the liver Hepatoerythropoietic porphyria, a blood disease High- ...
... porphyria cutanea tarda MeSH C06.552.830.437 - porphyria, hepatoerythropoietic MeSH C06.552.830.625 - porphyria, variegate MeSH ...
... porphyria cutanea tarda MeSH C18.452.872.617.400.437 - porphyria, hepatoerythropoietic MeSH C18.452.872.617.400.625 - porphyria ... porphyria cutanea tarda MeSH C18.452.648.735.437 - porphyria, hepatoerythropoietic MeSH C18.452.648.735.625 - porphyria, ... porphyrias MeSH C18.452.872.617.250 - porphyria, erythropoietic MeSH C18.452.872.617.400 - porphyrias, hepatic MeSH C18.452. ... porphyria, erythropoietic MeSH C18.452.648.735 - porphyrias, hepatic MeSH C18.452.648.735.074 - coproporphyria, hereditary MeSH ...
... porphyria cutanea tarda MeSH C16.320.565.735.437 - porphyria, hepatoerythropoietic MeSH C16.320.565.735.625 - porphyria, ... porphyria cutanea tarda MeSH C16.320.850.742.437 - porphyria, hepatoerythropoietic MeSH C16.320.850.742.625 - porphyria, ... porphyria, erythropoietic MeSH C16.320.565.735 - porphyrias, hepatic MeSH C16.320.565.735.074 - coproporphyria, hereditary MeSH ... porphyria, erythropoietic MeSH C16.320.850.742 - porphyrias, hepatic MeSH C16.320.850.742.074 - coproporphyria, hereditary MeSH ...
... porphyria cutanea tarda MeSH C17.800.849.617.400.437 - porphyria, hepatoerythropoietic MeSH C17.800.849.617.400.625 - porphyria ... porphyria cutanea tarda MeSH C17.800.827.742.437 - porphyria, hepatoerythropoietic MeSH C17.800.827.742.625 - porphyria, ... porphyrias MeSH C17.800.849.617.250 - porphyria, erythropoietic MeSH C17.800.849.617.400 - porphyrias, hepatic MeSH C17.800. ... porphyria, erythropoietic MeSH C17.800.827.742 - porphyrias, hepatic MeSH C17.800.827.742.074 - coproporphyria, hereditary MeSH ...
... autosomal recessive deafness 36 Hemochromatosis Hepatoerythropoietic porphyria Homocystinuria Hutchinson Gilford progeria ... Muckle-Wells syndrome Nonsyndromic deafness Oligodendroglioma Parkinson disease Pheochromocytoma porphyria porphyria cutanea ... the gene for porphyria cutanea tarda) USP1 (1p31) USP48: Ubiquitin carboxyl-terminal hydrolase 48 VAV3 (1p13) VPS13D: Vacuolar ... syndrome TAR syndrome trimethylaminuria Usher syndrome Usher syndrome type II Van der Woude syndrome Variegate porphyria G- ...
ISBN 978-0-7216-2921-6. "hepatoerythropoietic porphyria" at Dorlands Medical Dictionary Hepatoerythropoietic porphyria at NLM ... Hepatoerythropoietic porphyria is a very rare form of hepatic porphyria caused by a disorder in both genes which code ... In classifications which define PCT type 1 as "sporadic" and PCT type 2 as "familial", hepatoerythropoietic porphyria is more ... February 2007). "Two novel uroporphyrinogen decarboxylase (URO-D) mutations causing hepatoerythropoietic porphyria (HEP)". ...
Porphyria is a predominantly inherited metabolic disorder, resulting from a deficiency of an enzyme in the heme production ... porphyria cutanea tarda (PCT), and erythropoietic porphyria (EP) cause mostly cutaneous symptoms. Two porphyrias overlap these ... Porphyria Diagnostics-Part 1: A Brief Overview of the Porphyrias. Curr Protoc Hum Genet. 2015 Jul 1. 86:17.20.1-26. [QxMD ... Signs of cutaneous porphyria. Skin changes are the hallmark of the cutaneous porphyrias. They can be acute (CEP), with erythema ...
Porphyria is named from the ancient Greek word porphura, meaning purple. Porphyrins are precursors of heme, a part of the ... In porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP), the enzyme uroporphyrinogen decarboxylase is ... Types of porphyria. Porphyrias can be inherited or (rarely) acquired. [1] There are at least 8 different types of porphyrias. ... In porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP), the enzyme uroporphyrinogen decarboxylase is ...
Signs and symptoms of porphyrias are variable and nonspecific. Porphyrias are generally classified as either acute or cutaneous ... The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme ... ADP, ALA dehydratase-deficient porphyria; ALA, aminolevulinic acid; HEP, hepatoerythropoietic porphyria. Sources: Woolf , Karim ... The acute porphyrias (also referred to as acute hepatic porphyrias), which include acute intermittent porphyria (AIP), ...
... By Dr. Stephen Cohen. Read About Diseases, Conditions & Injuries. Free To Browse, Download ... Clinically symptoms are indistinguishable from hepatoerythropoietic porphyria.. ← Conductive hearing loss → Conjunctivitis ... Congenital erythropoietic porphyria. Rare inherited autosomal recessive disease with hemolytic anemia and marked skin ... Congenital erythropoietic porphyria is a rare, autosomal recessive disease caused by a mutation in the UROS gene, which encodes ...
Porphyrias with blistering cutaneous features include porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria. ... Hepatoerythropoietic porphyria - Childhood onset with rare autosomal recessive uroporphyrin decarboxylase deficiency.. * ... Porphyrias with nonblistering cutaneous features include erythropoietic protoporphyria and X-linked protoporphyria. Porphyrias ... Porphyria cutanea tarda Print Images (64) Contributors: Erin X. Wei MD, Lauren Ko, Belinda Tan MD, PhD, Susan Burgin MD. Other ...
... congenital erythropoietic porphyria, and hepatoerythropoietic porphyria. With the exception of acquired PCT, the porphyrias are ... congenital erythropoietic porphyria, hepatoerythropoietic porphyria, variegate porphyria, and hereditary coproporphyria).1,2 ... variegate porphyria, hereditary coproporphyria, and ALA-D-deficiency porphyria. The nonacute porphyrias include porphyria ... Hepatoerythropoietic porphyria is a rare autosomal- recessive porphyria attributable to a defect in UROD, which is the same ...
result sql = Hepatoerythropoietic porphyria. Hepatoerythropoietic porphyria 4. char = M;code = 77. char = e;code = 101. char = ... result sql = Porphyria. Porphyria 237. char = P;code = 80. char = o;code = 111. char = r;code = 114. char = p;code = 112. char ... result sql = Porphyria cutanea tarda. Porphyria cutanea tarda 45. char = s;code = 115. char = k;code = 107. char = i;code = 105 ... start str = Variegate porphyria. sql str = Variegate porphyria. start str = Hereditary coproporphyria. sql str = Hereditary ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Hepatoerythropoietic Porphyria Whats New Last Posted: Jan 01, 2011 * Hepatoerythropoietic porphyria From NCATS Genetic and ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
Porphyria, Erythrohepatic. Porphyria, Hepatoerythropoietic. Porphyria, Hepatic. Porphyrias, Hepatic. Stomach Dilatation. ...
United Porphyrias Association Scientific Advisory Board members research is focused on improving the lives of people with the ... Hepatoerythropoietic Porphyria. Gene Reviews, 2013. PMID 24175354. *Singal AK, Anderson KE: Porphyrias Consortium of the RDCRN ... Porphyria cutanea tarda and hepatoerythropoietic porphyria: Identification of 19 novel uroporphyrinogen III decarboxylase ... Singal, AK, Anderson KE: Porphyria cutanea tarda and hepatoerythropoietic porphyria. In: UpToDate, Rose, BD (Ed), UpToDate, ...
The acute or inducible hepatic porphyrias comprise four inherited disorders of heme biosynthesis. They usually remain ... This risk is increased in porphyria cutanea tarda, hepatoerythropoietic porphyria, and in all of the acute hepatic porphyrias, ... variegate porphyria; PCT, porphyria cutanea tarda; HEP, hepatoerythropoietic porphyria. ... variegate porphyria; PCT, porphyria cutanea tarda; HEP, hepatoerythropoietic porphyria. ...
Overview of Porphyrias - Explore from the MSD Manuals - Medical Consumer Version. ... Porphyria cutanea tarda Porphyria Cutanea Tarda Porphyria cutanea tarda is the most common porphyria and causes blistering and ... Hepatoerythropoietic porphyria (extremely rare). Skin becomes fragile and blistered, generally on sun-exposed areas (such as ... Acute intermittent porphyria Acute Intermittent Porphyria Acute intermittent porphyria, which causes abdominal pain and ...
Hepatoerythropoietic porphyria (57 occurrences). Hepatoma (8040 occurrences). Hepatopulmonary Syndrome (541 occurrences). ... Hepatoerythropoietic porphyria (57 occurrences). Mortons metatarsalgia (53 occurrences). Retractile mesenteritis (50 ... Porphyria (3127 occurrences). Porphyria cutanea tarda (1103 occurrences). Pouchitis (978 occurrences). pregnancy (9440 ... Porphyria (3127 occurrences). Pulmonary atresia (3127 occurrences). Senile dementia (3105 occurrences). Carotid stenting (3084 ...
Porphyria Panel Is ideal for patients with a clinical suspicion of porphyria. This panel is included in the Comprehensive ... Porphyria cutanea tarda, Porphyria, hepatoerythropoietic. AD/AR. 15. 122. UROS Porphyria, congenital erythropoietic. AR. 22. 49 ... Porphyria, acute intermittent, Hydroxymethylbilane synthase deficiency. AD/AR. 55. 419. PPOX Porphyria variegata. AD/AR. 16. ... About Porphyria Porphyrias are a group of metabolic disorders that are characterized by abnormalities in the production of heme ...
... hepatoerythropoietic porphyria, erythropoietic protoporphyria and hereditary spherocytosis, respectively (Brownlie et al., 1998 ...
Porphyria answers are found in the 5-Minute Clinical Consult powered by Unbound Medicine. Available for iPhone, iPad, Android, ... Hepatoerythropoietic porphyria (HEP) caused by biallelic UROD gene mutations (homozygous recessive; extremely rare) ... Acute intermittent porphyria. PORPHYRIA, ACUTE: LABORATORY EVALUATION OF SUSPECTED ACUTE NEUROVISCERAL OR NEUROCUTANEOUS ... Porphyria. (2020). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (27th ed ...
Approximately 80% of all cases of porphyria cutanea tarda are acquired; 20% are familial, although the ratio may vary among ... Porphyria cutanea tarda (PCT) is a term encompassing a group of acquired and familial disorders in which activity of the heme ... Hepatoerythropoietic porphyria: a new uroporphyrinogen decarboxylase defect or homozygous porphyria cutanea tarda?. Lancet. ... Hepatoerythropoietic porphyria: a missense mutation in the UROD gene is associated with mild disease and an unusual porphyrin ...
  • 525 It has a similar presentation to porphyria cutanea tarda (PCT), but with earlier onset. (wikipedia.org)
  • Aminolevulinic acid dehydrase (ALAD) porphyria and acute intermittent porphyria (AIP) cause predominately neurovisceral symptoms, whereas congenital erythropoietic porphyria (CEP), porphyria cutanea tarda (PCT), and erythropoietic porphyria (EP) cause mostly cutaneous symptoms. (medscape.com)
  • Phlebotomy and apheresis can remove excessive iron in patients with porphyria cutanea tarda (PCT). (medscape.com)
  • Acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and the familial form of porphyria cutanea tarda (PCT) follow an autosomal dominant inheritance pattern with low penetration. (medscape.com)
  • Cutaneous signs often result from photosensitivity (eg, skin fragility and blistering in porphyria cutanea tarda). (medscape.com)
  • Individuals with any of the cutaneous porphyrias, which include porphyria cutanea tarda (PCT), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and XLP, can experience photosensitivity as a result of sun exposure, which can manifest with either blisters and scarring or immediate redness and pain. (arupconsult.com)
  • It has the same clinical and histologic features as porphyria cutanea tarda (PCT) but does not cause biochemical porphyrin abnormalities. (arupconsult.com)
  • Porphyrias with blistering cutaneous features include porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria . (logicalimages.com)
  • The nonacute porphyrias include porphyria cutanea tarda (PCT), erythropoietic protoporphyria, congenital erythropoietic porphyria, and hepatoerythropoietic porphyria. (clinicaladvisor.com)
  • Gunn GB, Anderson KE, Patel AJ, Gallegos J, Hallberg C, Sood G, Hatch SS, Sanguineti, G: Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: case report and review of the literature. (porphyria.org)
  • Grady JJ, Lee C, Anderson KE, Associations among behavior-related susceptibility factors in porphyria cutanea tarda. (porphyria.org)
  • [ 55 ] A recent pilot study of the oral iron-chelating agent desferasirox in 10 patients with porphyria cutanea tarda found that 7 who completed the 6-month trial noted resolution of blistering, 6 had lesser urinary porphyrin content, and 7 had reduced serum ferritin levels. (medscape.com)
  • For patients with porphyria cutanea tarda who are anemic due to other chronic diseases (eg, renal failure, human immunodeficiency viral infection), human recombinant erythropoietin can be used to stimulate erythropoiesis. (medscape.com)
  • Pregnancy in women with porphyria cutanea tarda has been followed by safe delivery of healthy infants. (medscape.com)
  • [ 59 ] Mobilization of maternal excess tissue iron stores to support the growing fetus may actually be beneficial to pregnant women with porphyria cutanea tarda. (medscape.com)
  • Reinstitution of estrogenic hormone therapies in women with porphyria cutanea tarda who have achieved remissions may be completed in some cases without inducing the return of overt disease, but the risk of doing so must be balanced against the benefits of such therapies. (medscape.com)
  • If a patient accepts the risk (presently unquantifiable) of possibly reactivating her porphyria cutanea tarda in the hope of regaining the benefits of estrogen therapies, the use of transdermal delivery systems is recommended to mitigate the first-pass effects of oral estrogens reaching the liver from the enteric tract. (medscape.com)
  • Porphyria is not a single disease but a group of nine disorders: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), δ-aminolevulinic acid dehydratase deficiency porphyria (ADP), porphyria cutanea tarda (PCT), hepatoerythropoietic porphyria (HEP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and X-linked protoporphyria (XLP). (qxmd.com)
  • The Mount Sinai Genetic Testing Laboratory in New York City is proud to announce availability of DNA testing for seven Porphyrias, including Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), familial Porphyria Cutanea Tarda (f-PCT), Hepatoerythropoietic Porphyria (HEP), Erythropoietic Protoporphyria (EPP) and Congenital Erythropoietic Porphyria (CEP). (porphyriafoundation.org)
  • All porphyrias, except for sporadic porphyria cutanea tarda (sPCT), are hereditary disorders caused by mutations in the respective genes. (scienceopen.com)
  • Clinical features include neurological symptoms ( PORPHYRIA, ACUTE INTERMITTENT ), cutaneous lesions due to photosensitivity ( PORPHYRIA CUTANEA TARDA ), or both ( HEREDITARY COPROPORPHYRIA ). (nih.gov)
  • Two porphyrias overlap these categories and can cause both neurovisceral and cutaneous symptoms, namely hereditary coproporphyria (HCP) and variegate porphyria (VP). (medscape.com)
  • Porphyria is the common term for a group of syndromes, largely hereditary, that result from defects in porphyrins (the enzymes involved in heme synthesis). (medscape.com)
  • The acute porphyrias (also referred to as acute hepatic porphyrias), which include acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP), are characterized by neurovisceral attacks that can cause neurologic damage and death if not treated promptly. (arupconsult.com)
  • Lead poisoning and hereditary tyrosinemia type I can cause neuropathies similar to those of acute intermittent porphyria (AIP), as well as elevated porphyrins and aminolevulinic acid (ALA). Conditions with similar presentations to AIP but without elevated porphobilinogen (PBG) excretions include Guillain-Barré syndrome and seizures. (arupconsult.com)
  • Porphyrias that can have both blistering cutaneous features and acute neurovisceral attacks include hereditary coproporphyria and variegate porphyria (VP). (logicalimages.com)
  • The acute porphyrias include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and ALA-D-deficiency porphyria. (clinicaladvisor.com)
  • Also included in the differential are the other porphyrias that present with blistering (congenital erythropoietic porphyria, hepatoerythropoietic porphyria, variegate porphyria, and hereditary coproporphyria). (clinicaladvisor.com)
  • The four disorders are ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. (ashpublications.org)
  • Other conditions that clinically and biochemically may mimic acute porphyria include lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these acute porphyric syndromes should be considered in many patients with otherwise unexplained abdominal pain, severe constipation, systemic arterial hypertension, or other characteristic symptoms. (ashpublications.org)
  • Some acute porphyrias (variegate porphyria and hereditary coproporphyria) may also cause skin (cutaneous) symptoms. (msdmanuals.com)
  • Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms. (nih.gov)
  • Mutation analysis was performed in patients/families with a confirmed hereditary porphyria. (scienceopen.com)
  • A total of 217 patients from 170 families were diagnosed including, 111 acute intermittent porphyria, 45 erythropoietic protoporphyria, 30 variegate porphyria, 21 sPCT, five congenital erythropoietic porphyria, four hereditary coproporphyria and one hepatoerythropoietic porphyria patient. (scienceopen.com)
  • Hepatic porphyrias can be hereditary or acquired as a result of toxicity to the hepatic tissues. (nih.gov)
  • Hereditary coproporphyria (HCP) is a form of hepatic porphyria associated with a deficiency of the enzyme coproporphyrinogen III oxidase. (bionity.com)
  • Demonstration of elevated porphyrins in plasma (particularly for congenital erythropoietic porphyria [CEP]), urine, and stool is very useful for diagnosis of the porphyrias. (medscape.com)
  • Aminolevulinic acid dehydratase deficiency porphyria (ADP), congenital erythropoietic porphyria (CEP), erythropoietic protoporphyria (EPP), and hepatoerythropoietic porphyria (HEP) are autosomal recessive. (medscape.com)
  • Congenital erythropoietic porphyria is a rare, autosomal recessive disease caused by a mutation in the UROS gene, which encodes uroporphyrinogen III synthase. (standardofcare.com)
  • The classic primary manifestation of congenital erythropoietic porphyria is pink-red discoloration of the urine in infancy or childhood. (standardofcare.com)
  • Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. (nih.gov)
  • Porphyria is a predominantly inherited metabolic disorder resulting from a deficiency of an enzyme in the heme production pathway and overproduction of toxic heme precursors. (medscape.com)
  • Porphyrias with only neurovisceral symptoms without skin findings include acute intermittent porphyria and delta-aminolevulinic acid (ALA) dehydratase deficiency porphyria. (logicalimages.com)
  • Each of the porphyrias is due to the deficiency of a specific enzyme involved in heme synthesis. (ashpublications.org)
  • Porphyrias are a group of different disorders, each caused by a deficiency in one of the enzymes needed for heme production. (msdmanuals.com)
  • Each porphyria results from overproduction of heme precursors secondary to partial deficiency or, in XLP, increased activity of one of the enzymes of heme biosynthesis. (qxmd.com)
  • Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. (nih.gov)
  • An autosomal dominant or acquired porphyria due to a deficiency of UROPORPHYRINOGEN DECARBOXYLASE in the LIVER . (nih.gov)
  • Variegate porphyria (VP) - May present with skin findings identical to PCT, but patients are also at risk for acute porphyric neurologic crises not seen in PCT. (logicalimages.com)
  • See more studies on Variegate porphyria and. (naturalnews.com)
  • [ 2 ] There is also an X-linked dominant inherited porphyria called X-linked protoporphyria (XLP). (medscape.com)
  • The porphyrias are caused by loss (or gain, in the case of X-linked erythropoietic protoporphyria [XLP]) of specific enzyme functions in the heme biosynthesis pathway. (arupconsult.com)
  • Porphyrias with nonblistering cutaneous features include erythropoietic protoporphyria and X-linked protoporphyria . (logicalimages.com)
  • For explanation of diagnosis and management of the acute porphyrias and the acute manifestations of porphyrias with both neurovisceral and cutaneous components, please refer to the companion article Porphyria, Acute . (medscape.com)
  • Downregulation of ALA synthase-1 by avoidance or removal of inducing drugs and chemicals by nutritional means (high carbohydrate intakes) and by administration of exogenous heme remains the cornerstone of management of the acute porphyrias. (ashpublications.org)
  • 2023 United Porphyrias Association All Rights Reserved. (porphyria.org)
  • Hepatoerythropoietic porphyria is a very rare form of hepatic porphyria caused by a disorder in both genes which code Uroporphyrinogen III decarboxylase (UROD). (wikipedia.org)
  • The t wo current classifications of porphyria are: acute hepatic porphyria (AHP), and erythropoietic porphyria (EP). (porphyriaalliance.org)
  • The main focus of this article is put on acute (hepatic) porphyria (AHP). (scienceopen.com)
  • Hepato-erythropoietic porphyria presenting as scleroderma and acrosclerosis in a sibling pair. (pte.hu)
  • The mutations that underlie porphyria result in accumulation and increased excretion of porphyrins and their precursors. (medscape.com)
  • In these porphyrias, certain porphyrins are deposited in the skin. (msdmanuals.com)
  • Porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized by excessive accumulation and excretion of porphyrins and their precursors. (qxmd.com)
  • The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. (nih.gov)
  • Porphyrias are divided into two types according to the predominant symptoms: (1) the neurovisceral or acute porphyrias, with abdominal pain, neuropathy, autonomic instability, and psychosis, and (2) the cutaneous porphyrias, with symptoms of photosensitive lesions on the skin. (medscape.com)
  • Depending on the specific enzyme affected, porphyria may manifest clinically in an acute or non-acute manner, and the signs and symptoms may be predominantly neurovisceral, psychiatric, cutaneous, or some combination of those. (medscape.com)
  • Signs and symptoms of porphyrias are variable and nonspecific. (arupconsult.com)
  • Porphyrias are generally classified as either acute or cutaneous, but some types can have overlapping symptoms, which can complicate diagnosis. (arupconsult.com)
  • Diagnostic testing for porphyrias should be performed in individuals who present with severe, diffuse neuropathic abdominal pain and accompanying symptoms and in individuals with cutaneous photosensitivity. (arupconsult.com)
  • Clinically symptoms are indistinguishable from hepatoerythropoietic porphyria. (standardofcare.com)
  • The accumulated heme precursors cause symptoms and can often be detected by testing to help diagnose porphyria. (msdmanuals.com)
  • Acute porphyrias cause intermittent attacks of abdominal, mental health, and neurologic symptoms. (msdmanuals.com)
  • Some cutaneous porphyrias cause symptoms that tend to be continuous or intermittent. (msdmanuals.com)
  • Porphyrias present with neuro-visceral symptoms, skin problems, or both. (blueprintgenetics.com)
  • Acute porphyrias usually have nerve symptoms and episodic crises resulting in nausea, vomiting, abdominal pain and hypertension. (blueprintgenetics.com)
  • Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. (nih.gov)
  • Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. (nih.gov)
  • Diagnosis of the specific Porphyria can be difficult because the three acute Hepatic Porphyrias (AIP, HCP, VP) typically have similar acute symptoms, biochemical findings, and responses to treatment. (porphyriafoundation.org)
  • For patients with symptoms of an acute Porphyria, but without a specific diagnosis, we offer a 'triple test,' which includes DNA testing for the three major acute hepatic Porphyrias (AIP, HCP, and VP). (porphyriafoundation.org)
  • Beta-carotene is a pigment found in various green and yellow fruits and vegetables and can decrease the severity of photosensitivity reactions in patients with porphyria. (medscape.com)
  • A common symptom of acute porphyrias is severe acute abdominal pain, whereas cutaneous photosensitivity can occur in both acute and non-acute porphyrias. (scienceopen.com)
  • The United Porphyrias Association web pages are designed for educational purposes only and not for the purpose of rendering medical advice. (porphyria.org)
  • As shown in Figure 1 , there is no porphyria associated with a defect in ALA synthase-1, but mutations of the X-linked ALA synthase-2 (the erythroid form) are causative for X-linked sideroblastic anemia. (ashpublications.org)
  • In the Porphyrias, there are no common mutations so the entire gene must be sequenced in each new family. (porphyriafoundation.org)
  • Urine porphyrin studies are the mainstay in the diagnosis of acute porphyria attacks. (medscape.com)
  • Avoidance of sunlight is the key in preventing attacks of cutaneous porphyrias. (medscape.com)
  • The acute porphyrias are characterized by potentially life-threatening neurologic attacks that do not occur in the nonacute porphyrias. (clinicaladvisor.com)
  • The treatment of choice for all but mild attacks of the acute porphyrias is intravenous hemin therapy, which should be started as soon as possible. (ashpublications.org)
  • Non-acute porphyrias seldom have acute attacks but rather cause skin problems after exposure to light as these molecules react with light. (blueprintgenetics.com)
  • because these two types, HCP, and VP, are documented to not have urinary elevations in ALA/ PBG during life threatening attacks (Hematin treatment of Acute Porphyria, Peterson, 1976) (Janus, 2017). (porphyriaalliance.org)
  • Acute attacks usually require hospitalisation and treatment by a porphyria specialist. (porphyria-australia.org)
  • There are 2 and possibly many more known sub types of porphyria so far, HEP, a dual PCT, and Chester Porphyria a VP/ AIP hybrid. (porphyriaalliance.org)
  • Other types of porphyria, called acute porphyrias, primarily affect the nervous system. (nih.gov)
  • Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. (nih.gov)
  • Porphyrias are a group of metabolic disorders that are characterized by abnormalities in the production of heme and result in the accumulation of heme precursors in the liver or in the bone marrow and blood cells. (blueprintgenetics.com)
  • In erythropoietic porphyrias, these compounds originate in the bone marrow. (nih.gov)
  • Taken together, all forms of porphyria afflict fewer than 200,000 people in the United States. (qxmd.com)
  • In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific Porphyria and is considered the 'gold standard' for the diagnosis of genetic disorders. (porphyriafoundation.org)
  • AIP is an acute porphyria known to cause abdominal pain, gastrointestinal issues, and neurological changes. (porphyria-australia.org)
  • The porphyrias are metabolic diseases caused by deficiencies in enzymes involved in the heme biosynthetic pathway. (clinicaladvisor.com)
  • A normal urine PBG result has a sensitivity of almost 100% (ie, rules out) in the diagnosis of porphyria in acutely symptomatic patients. (medscape.com)
  • An accurate and prompt diagnosis is important during an acute attack of an acute porphyria because delayed treatment can cause permanent damage or death. (arupconsult.com)
  • What is the role of skin biopsy in the diagnosis of porphyrias? (arupconsult.com)
  • Its important to confirm the diagnosis of porphyria and to document this clearly in the patient records and plan. (porphyria-australia.org)
  • If a mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. (porphyriafoundation.org)
  • Thus, the diagnosis of a specific Porphyria determines what gene to test. (porphyriafoundation.org)
  • This means, for example, that if a patient has been given the diagnosis of AIP and no AIP gene mutation is identified, it is possible that the patient has a different acute Porphyria. (porphyriafoundation.org)
  • As the porphyria specialist centre of Switzerland, we perform the specialized analyses required for the diagnosis of all types of porphyrias, and give advice to patients, physicians and other laboratories. (scienceopen.com)
  • The other enzymes, when deficient, give rise to the types of porphyrias shown in Tables 1 Table 1A , Table 1B and 2 . (ashpublications.org)
  • Identification of pre-symptomatic mutation carriers so that these individuals and their physicians can be consulted with safety on drug use and other preventive measures, is important in managing acute porphyrias. (scienceopen.com)
  • The cutaneous porphyrias are dermatologic diseases that may or may not involve the liver and nervous system. (medscape.com)
  • Porphyrias are a group of diseases resulting from defects / dysfunction in enzymes involved in heme biosynthesis. (logicalimages.com)
  • With the exception of acquired PCT, the porphyrias are inherited diseases. (clinicaladvisor.com)
  • The current porphyria literature is very exhaustive and a brief overview of porphyria diseases is essential in order for the reader to better appreciate the relevance of this area of research prior to undertaking biochemical diagnostics procedures. (qxmd.com)
  • This unit summarizes the current knowledge on the classification, clinical features, etiology, pathogenesis, and genetics of porphyria diseases. (qxmd.com)
  • Clinical classification of the different porphyrias. (medscape.com)
  • Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias. (nih.gov)
  • Systematic monitoring of the patients would allow early detection of the potential life-threatening complications such as hepatocellular carcinoma and renal insufficiency in acute porphyrias, and liver failure in EPP. (scienceopen.com)
  • Once a mutation has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that Porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications. (porphyriafoundation.org)
  • Each Porphyria is caused by a mutation in the DNA sequence of a specific gene. (porphyriafoundation.org)
  • In classifications which define PCT type 1 as "sporadic" and PCT type 2 as "familial", hepatoerythropoietic porphyria is more similar to type 2. (wikipedia.org)
  • What are potential complications for patients with acute hepatic porphyrias? (arupconsult.com)
  • Patients with acute hepatic porphyrias are at greater risk for hepatic fibrosis or cirrhosis, as well as hepatocellular carcinoma (HCC). (arupconsult.com)
  • Is ideal for patients with a clinical suspicion of porphyria. (blueprintgenetics.com)
  • We thank the Porphyria patients who sent us their blood to develop and validate these tests. (porphyriafoundation.org)
  • Medicine Central , im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/816140/all/Porphyria. (unboundmedicine.com)