A genetic metabolic disorder resulting from serum and bone alkaline phosphatase deficiency leading to hypercalcemia, ethanolamine phosphatemia, and ethanolamine phosphaturia. Clinical manifestations include severe skeletal defects resembling vitamin D-resistant rickets, failure of the calvarium to calcify, dyspnea, cyanosis, vomiting, constipation, renal calcinosis, failure to thrive, disorders of movement, beading of the costochondral junction, and rachitic bone changes. (From Dorland, 27th ed)
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.
Inorganic salts of phosphoric acid that contain two phosphate groups.
The process whereby calcium salts are deposited in the dental enamel. The process is normal in the development of bones and teeth. (Boucher's Clinical Dental Terminology, 4th ed, p43)
Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., GLUCOSYLCERAMIDASE replacement for GAUCHER DISEASE).
A group of phosphate minerals that includes ten mineral species and has the general formula X5(YO4)3Z, where X is usually calcium or lead, Y is phosphorus or arsenic, and Z is chlorine, fluorine, or OH-. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Disorder caused by an interruption of the mineralization of organic bone matrix leading to bone softening, bone pain, and weakness. It is the adult form of rickets resulting from disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis.
An inorganic pyrophosphate which affects calcium metabolism in mammals. Abnormalities in its metabolism occur in some human diseases, notably HYPOPHOSPHATASIA and pseudogout (CHONDROCALCINOSIS).
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).
Disorders caused by interruption of BONE MINERALIZATION manifesting as OSTEOMALACIA in adults and characteristic deformities in infancy and childhood due to disturbances in normal BONE FORMATION. The mineralization process may be interrupted by disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.

Correlations of genotype and phenotype in hypophosphatasia. (1/78)

Hypophosphatasia, a rare inherited disorder characterized by defective bone mineralization, is highly variable in its clinical expression. The disease is due to various mutations in the tissue-non-specific alkaline phosphatase ( TNSALP ) gene. We report here the use of clinical data, site-directed mutagenesis and computer-assisted modelling to propose a classification of 32 TNSALP gene mutations found in 23 European patients, 17 affected with lethal hypophosphatasia and six with non-lethal hypophosphatasia. Transfection studies of the missense mutations found in non-lethal hypophosphatasia showed that six of them allowed significant residual in vitro enzymatic activity, suggesting that these mutations corresponded to moderate alleles. Each of the six patients with non-lethal hypophosphatasia carried at least one of these alleles. The three-dimensional model study showed that moderate mutations were not found in the active site, and that most of the severe missense mutations were localized in crucial domains such as the active site, the vicinity of the active site and homodimer interface. Some mutations appeared to be organized in clusters on the surface of the molecule that may represent possible candidates for regions interacting with the C-terminal end involved in glycosylphosphatidylinositol (GPI) attachment or with other dimers to form tetramers. Finally, our results show a good correlation between clinical forms of the disease, mutagenesis experiments and the three-dimensional structure study, and allowed us to clearly distinguish moderate alleles from severe alleles. They also confirm that the extremely high phenotypic heterogeneity observed in patients with hypophosphatasia was due mainly to variable residual enzymatic activities allowed by missense mutations found in the human TNSALP gene.  (+info)

Hypophosphatasia: diagnostic application of linked DNA markers in the dominantly inherited adult form. (2/78)

Hypophosphatasia is a rare disease characterized by low serum levels of tissue non-specific alkaline phosphatase (TNSALP) and a spectrum of skeletal disease varying from the severest form with death in utero to mild with no clinical abnormality in adults. Currently, the diagnosis of hypophosphatasia is made on the basis of clinical findings, radiography, low serum alkaline phosphatase levels and raised abnormal phosphorylated metabolites; there are elevations in serum pyridoxal 5'-phosphate, urinary phosphoethanolamine and inorganic pyrophosphate. In borderline cases the biochemical diagnosis remains uncertain. Prenatally, diagnosis is made using radiography and ultrasonography together with chorionic villus tissue biopsy, in which TNSALP levels are measured using an antibody-based assay. Since hypophosphatasia results from mutations in the TNSALP gene we have, for the first time in two U.K. families, undertaken restriction fragment length polymorphism (RFLP) analysis using three intragenic RFLPs for BclI and MspI at the ALPL locus. One family was informative, and a mutant-allele-specific haplotype with respect to three RFLPs was defined. In the other family the disease was shown to segregate with one allele of the BclI RFLP, but the MspI RFLPs were not informative. The disease segregated in the two families with different alleles of the BclI RFLP, suggesting that the mutations are likely to be different. We confirm that DNA analysis is likely to be the way ahead for diagnosing hypophosphatasia, and that standardized screening methods need to be developed for detecting mutations in these and other families.  (+info)

Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. (3/78)

Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (-/-) had < 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of approximately 50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at approximately 10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.  (+info)

Possible interference between tissue-non-specific alkaline phosphatase with an Arg54-->Cys substitution and acounterpart with an Asp277-->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia. (4/78)

Tissue-non-specific alkaline phosphatase (TNSALP) with an Arg(54)-->Cys (R54C) or an Asp(277)-->Ala (D277A)substitution was found in a patient with hypophosphatasia [Henthorn,Raducha, Fedde, Lafferty and Whyte (1992) Proc. Natl. Acad. Sci. U.S.A.89, 9924-9928]. To examine effects of these missense mutations onproperties of TNSALP, the TNSALP mutants were expressed ectopically inCOS-1 cells. The wild-type TNSALP was synthesized as a 66-kDa endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive form, and processed to an 80-kDa mature form, which is anchored to the plasma membrane via glycosylphosphatidylinositol (GPI). Although the mutant proteins were found to be modified by GPI, digestion with phosphatidylinositol-specific phospholipase C, cell-surface biotinylation and immunofluorescence observation demonstrated that the cell-surface appearance of TNSALP (R54C) and TNSALP (D277A) was either almost totally or partially retarded respectively. The 66-kDa Endo H-sensitive band was the only form, and was rapidly degraded in the cells expressing TNSALP (R54C). In contrast with cells expressing TNSALP(R54C), where alkaline phosphatase activity was negligible, significant enzyme activity was detected and, furthermore, the 80-kDa mature form appeared on the surface of the cells expressing TNSALP (D277A). Analysis by sedimentation on sucrose gradients showed that a considerable fraction of newly synthesized TNSALP (R54C) and TNSALP(D277A) formed large aggregates, indicating improper folding and incorrect oligomerization of the mutant enzymes. When co-expressed with TNSALP (R54C), the level of the 80-kDa mature form of TNSALP (D277A)was decreased dramatically, with a concomitant reduction in enzyme activity in the co-transfected cell. These findings suggest that TNSALP(R54C) interferes with folding and assembly of TNSALP (D277A) intrans when expressed in the same cell, thus probably explaining why a compound heterozygote for these mutant alleles developed severe hypophosphatasia.  (+info)

Early prenatal sonographic diagnosis of congenital hypophosphatasia. (5/78)

A pregnant woman of 14 weeks' gestation was sonographically examined due to large-for-dates uterine size. The ultrasound examination showed poor ossification of all bony structures. All limbs were shortened with no evidence of fractures. The echodensity approximated that of the surrounding organs. No acoustic shadowing was observed. Based on these sonographic findings, skeletal dysplasia and short-limb dwarfism were diagnosed, the most likely condition being congenital hypophosphatasia. Early cordocentesis was successfully performed at 15 weeks' gestation to determine fetal alkaline phosphatase concentration. This was undetectable. The prenatal diagnosis of congenital hypophosphatasia was made. After counselling, the woman decided to opt for termination of pregnancy which was performed vaginally. Post-abortion findings confirmed the prenatal diagnosis. To our knowledge, this is the earliest sonographic diagnosis of this condition reported.  (+info)

Biosynthesis of phosphatidylcholine from a phosphocholine precursor pool derived from the late endosomal/lysosomal degradation of sphingomyelin. (6/78)

Previous studies suggest that the steps of the CDP- choline pathway of phosphatidylcholine synthesis are tightly linked in a so-called metabolon. Evidence has been presented that only choline that enters cells through the choline transporter, and not phosphocholine administered to cells by membrane permeabilization, is incorporated into phosphatidylcholine. Here, we show that [(14)C]phosphocholine derived from the lysosomal degradation of [(14)C]choline-labeled sphingomyelin is incorporated as such into phosphatidylcholine in human and mouse fibroblasts. Low density lipoprotein receptor-mediated endocytosis was used to specifically direct [(14)C]sphingomyelin to the lysosomal degradation pathway. Free labeled choline was not found either intracellularly or in the medium, not even when the cells were energy-depleted. Deficiency of lysosomal acid phosphatases in mouse or alkaline phosphatase in human fibroblasts did not affect the incorporation of lysosomal [(14)C]sphingomyelin-derived [(14)C]phosphocholine into phosphatidylcholine, supporting our finding that phosphocholine is not degraded to choline prior to its incorporation into phosphatidylcholine. Inhibition studies and analysis of molecular species showed that exogenous [(3)H]choline and sphingomyelin-derived [(14)C]phosphocholine are incorporated into phosphatidylcholine via a common pathway of synthesis. Our findings provide evidence that, in fibroblasts, phosphocholine derived from sphingomyelin is transported out of the lysosome and subsequently incorporated into phosphatidylcholine without prior hydrolysis of phosphocholine to choline. The findings do not support the existence of a phosphatidylcholine synthesis metabolon in fibroblasts.  (+info)

Retention at the cis-Golgi and delayed degradation of tissue-non-specific alkaline phosphatase with an Asn153-->Asp substitution, a cause of perinatal hypophosphatasia. (7/78)

Tissue-non-specific alkaline phosphatase (TNSALP) is an ectoenzyme anchored to the plasma membrane via glycosylphosphatidylinositol (GPI). A TNSALP mutant with an Asn(153)-->Asp (N153D) substitution was reported in a foetus diagnosed with perinatal hypophosphatasia (Mornet, Taillandier, Peyramaure, Kaper, Muller, Brenner, Bussiere, Freisinger, Godard, Merrer et al. (1998) Eur. J. Hum. Genet. 6, 308-314). When expressed ectopically in COS-1 cells, the wild-type TNSALP formed active non-covalently associated dimers, whereas TNSALP (N153D) formed aberrant disulphide-bonded high-molecular-mass aggregates devoid of enzyme activity. Cell-surface biotinylation and digestion with phosphatidylinositol-specific phospholipase C showed that TNSALP (N153D) failed to reach the cell surface. Instead, double immunofluorescence demonstrated that TNSALP (N153D) partially co-localized with a cis-Golgi marker (GM-130) at the steady-state. Upon treatment with brefeldin A, TNSALP (N153D) was still co-localized with GM-130, further supporting the finding that this mutant is localized in the cis-Golgi. Consistent with morphological results, pulse-chase experiments showed that newly synthesized TNSALP (N153D) remained endo-beta-N-acetylglucosaminidase H-sensitive throughout the chase. Eventually, after a prolonged chase time, the mutant was found to be partly degraded in a proteasome-dependent manner. Since the mutant TNSALP was significantly labelled with [3H]ethanolamine, a component of GPI, comparable with the wild-type enzyme, it is unlikely that the abortive synthesis of the mutant is due to a defect in GPI-attachment. Interestingly, when asparagine was replaced by glutamine at position 153 (N153D), TNSALP (N153Q) was indistinguishable from the wild-type enzyme in terms of its molecular properties, suggesting the possible importance of amino acids with a polar amide group at position 153. Taken together, these findings indicate that replacing asparagine with aspartic acid at position 153 causes misfolding and incorrect assembly of TNSALP, which results in its retention at the cis-Golgi en route to the cell surface, followed by a delayed degradation, presumably as part of a quality-control process. We postulate that the molecular basis of the perinatal hypophosphatasia associated with TNSALP (N153D) is due to the absence of mature TNSALP at the cell surface.  (+info)

Hypophosphatasia associated with increased nuchal translucency: a report of two affected pregnancies. (8/78)

Perinatal hypophosphatasia is a lethal autosomal recessive skeletal abnormality with a birth prevalence of about 1 per 100 000. It is characterized by deficiency of the tissue-nonspecific isoenzyme of alkaline phosphatase causing abnormal bone mineralization. In the two affected fetuses from the same family ultrasound examination at 14 and 12 weeks, respectively, demonstrated increased nuchal translucency thickness, hypomineralization of the skull and spine, narrowing of the chest and shortening of the limbs.  (+info)

Hypophosphatasia is a rare inherited metabolic disorder characterized by defective bone mineralization due to deficiency of alkaline phosphatase, an enzyme that is crucial for the formation of strong and healthy bones. This results in skeletal abnormalities, including softening and weakening of the bones (rickets in children and osteomalacia in adults), premature loss of teeth, and an increased risk of fractures.

The disorder can vary widely in severity, from mild cases with few symptoms to severe forms that can lead to disability or even be life-threatening in infancy. Hypophosphatasia is caused by mutations in the ALPL gene, which provides instructions for making the tissue non-specific alkaline phosphatase (TNSALP) enzyme. Inheritance is autosomal recessive, meaning an individual must inherit two copies of the mutated gene (one from each parent) to have the condition.

Alkaline phosphatase (ALP) is an enzyme found in various body tissues, including the liver, bile ducts, digestive system, bones, and kidneys. It plays a role in breaking down proteins and minerals, such as phosphate, in the body.

The medical definition of alkaline phosphatase refers to its function as a hydrolase enzyme that removes phosphate groups from molecules at an alkaline pH level. In clinical settings, ALP is often measured through blood tests as a biomarker for various health conditions.

Elevated levels of ALP in the blood may indicate liver or bone diseases, such as hepatitis, cirrhosis, bone fractures, or cancer. Therefore, physicians may order an alkaline phosphatase test to help diagnose and monitor these conditions. However, it is essential to interpret ALP results in conjunction with other diagnostic tests and clinical findings for accurate diagnosis and treatment.

Diphosphates, also known as pyrophosphates, are chemical compounds that contain two phosphate groups joined together by an oxygen atom. The general formula for a diphosphate is P~PO3~2-, where ~ represents a bond. Diphosphates play important roles in various biological processes, such as energy metabolism and cell signaling. In the context of nutrition, diphosphates can be found in some foods, including milk and certain vegetables.

Tooth calcification, also known as dental calculus or tartar formation, refers to the hardening of plaque on the surface of teeth. This process occurs when minerals from saliva combine with bacterial deposits and dental plaque, resulting in a hard, calcified substance that adheres to the tooth surface. Calcification can occur both above and below the gum line, and if not removed through professional dental cleanings, it can lead to periodontal disease, tooth decay, and other oral health issues.

Enzyme Replacement Therapy (ERT) is a medical treatment approach in which functional copies of a missing or deficient enzyme are introduced into the body to compensate for the lack of enzymatic activity caused by a genetic disorder. This therapy is primarily used to manage lysosomal storage diseases, such as Gaucher disease, Fabry disease, Pompe disease, and Mucopolysaccharidoses (MPS), among others.

In ERT, the required enzyme is produced recombinantly in a laboratory using biotechnological methods. The purified enzyme is then administered to the patient intravenously at regular intervals. Once inside the body, the exogenous enzyme is taken up by cells, particularly those affected by the disorder, and helps restore normal cellular functions by participating in essential metabolic pathways.

ERT aims to alleviate disease symptoms, slow down disease progression, improve quality of life, and increase survival rates for patients with lysosomal storage disorders. However, it does not cure the underlying genetic defect responsible for the enzyme deficiency.

Apatite is a group of phosphate minerals, primarily consisting of fluorapatite, chlorapatite, and hydroxylapatite. They are important constituents of rocks and bones, and they have a wide range of applications in various industries. In the context of medicine, apatites are most notable for their presence in human teeth and bones.

Hydroxylapatite is the primary mineral component of tooth enamel, making up about 97% of its weight. It provides strength and hardness to the enamel, enabling it to withstand the forces of biting and chewing. Fluorapatite, a related mineral that contains fluoride ions instead of hydroxyl ions, is also present in tooth enamel and helps to protect it from acid erosion caused by bacteria and dietary acids.

Chlorapatite has limited medical relevance but can be found in some pathological calcifications in the body.

In addition to their natural occurrence in teeth and bones, apatites have been synthesized for various medical applications, such as bone graft substitutes, drug delivery systems, and tissue engineering scaffolds. These synthetic apatites are biocompatible and can promote bone growth and regeneration, making them useful in dental and orthopedic procedures.

Osteomalacia is a medical condition characterized by the softening of bones due to defective bone mineralization, resulting from inadequate vitamin D, phosphate, or calcium. It mainly affects adults and is different from rickets, which occurs in children. The primary symptom is bone pain, but muscle weakness can also occur. Prolonged osteomalacia may lead to skeletal deformities and an increased risk of fractures. Treatment typically involves supplementation with vitamin D, calcium, and sometimes phosphate.

Calcium pyrophosphate is a mineral compound made up of calcium and pyrophosphate ions. In the body, it can form crystals that deposit in joints, causing a type of arthritis known as calcium pyrophosphate deposition (CPPD) disease or pseudogout. CPPD disease is characterized by sudden attacks of joint pain and swelling, often in the knee or wrist. The condition is more common in older adults and can also occur in people with underlying medical conditions such as hyperparathyroidism, hemochromatosis, and hypophosphatasia. Calcium pyrophosphate crystals may also be found in the fluid around the heart (pericardial fluid) or in other tissues, but they do not always cause symptoms.

Physiologic calcification is the normal deposit of calcium salts in body tissues and organs. It is a natural process that occurs as part of the growth and development of the human body, as well as during the repair and remodeling of tissues.

Calcium is an essential mineral that plays a critical role in many bodily functions, including bone formation, muscle contraction, nerve impulse transmission, and blood clotting. In order to maintain proper levels of calcium in the body, excess calcium that is not needed for these functions may be deposited in various tissues as a normal part of the aging process.

Physiologic calcification typically occurs in areas such as the walls of blood vessels, the lungs, and the heart valves. While these calcifications are generally harmless, they can sometimes lead to complications, particularly if they occur in large amounts or in sensitive areas. For example, calcification of the coronary arteries can increase the risk of heart disease, while calcification of the lung tissue can cause respiratory symptoms.

It is important to note that pathologic calcification, on the other hand, refers to the abnormal deposit of calcium salts in tissues and organs, which can be caused by various medical conditions such as chronic kidney disease, hyperparathyroidism, and certain infections. Pathologic calcification is not a normal process and can lead to serious health complications if left untreated.

Pyridoxal phosphate (PLP) is the active form of vitamin B6 and functions as a cofactor in various enzymatic reactions in the human body. It plays a crucial role in the metabolism of amino acids, carbohydrates, lipids, and neurotransmitters. Pyridoxal phosphate is involved in more than 140 different enzyme-catalyzed reactions, making it one of the most versatile cofactors in human biochemistry.

As a cofactor, pyridoxal phosphate helps enzymes carry out their functions by facilitating chemical transformations in substrates (the molecules on which enzymes act). In particular, PLP is essential for transamination, decarboxylation, racemization, and elimination reactions involving amino acids. These processes are vital for the synthesis and degradation of amino acids, neurotransmitters, hemoglobin, and other crucial molecules in the body.

Pyridoxal phosphate is formed from the conversion of pyridoxal (a form of vitamin B6) by the enzyme pyridoxal kinase, using ATP as a phosphate donor. The human body obtains vitamin B6 through dietary sources such as whole grains, legumes, vegetables, nuts, and animal products like poultry, fish, and pork. It is essential to maintain adequate levels of pyridoxal phosphate for optimal enzymatic function and overall health.

Rickets is a medical condition characterized by the softening and weakening of bones in children, primarily caused by deficiency of vitamin D, calcium, or phosphate. It leads to skeletal deformities, bone pain, and growth retardation. Prolonged lack of sunlight exposure, inadequate intake of vitamin D-rich foods, or impaired absorption or utilization of vitamin D can contribute to the development of rickets.

Ethanolamines are a class of organic compounds that contain an amino group (-NH2) and a hydroxyl group (-OH) attached to a carbon atom. They are derivatives of ammonia (NH3) in which one or two hydrogen atoms have been replaced by a ethanol group (-CH2CH2OH).

The most common ethanolamines are:

* Monethanolamine (MEA), also called 2-aminoethanol, with the formula HOCH2CH2NH2.
* Diethanolamine (DEA), also called 2,2'-iminobisethanol, with the formula HOCH2CH2NHCH2CH2OH.
* Triethanolamine (TEA), also called 2,2',2''-nitrilotrisethanol, with the formula N(CH2CH2OH)3.

Ethanolamines are used in a wide range of industrial and consumer products, including as solvents, emulsifiers, detergents, pharmaceuticals, and personal care products. They also have applications as intermediates in the synthesis of other chemicals. In the body, ethanolamines play important roles in various biological processes, such as neurotransmission and cell signaling.

... is considered particularly rare in people of African ancestry in the U.S. Hypophosphatasia is often discovered ... "Hypophosphatasia Signs and Symptoms". Hypophosphatasia.com. Archived from the original on 15 October 2014. Retrieved 10 ... "Hypophosphatasia". Genetics Home Reference. "Hypophosphatasia". NORD (National Organization for Rare Disorders). Retrieved 2020 ... but not adult hypophosphatasia. Perinatal hypophosphatasia is the most lethal form. Profound hypomineralization results in ...
"hypophosphatasia". Genetics Home Reference. Andrews, James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of ... Fracture Giant cell tumor of bone Greenstick fracture Gout Hypophosphatasia Hereditary multiple exostoses Klippel-Feil syndrome ...
"Hypophosphatasia Case Studies: Dangers of Misdiagnosis". Hypophosphatasia.com. Archived from the original on 8 August 2014. ... Mornet E, Nunes ME (20 November 2007). "Hypophosphatasia". GeneReviews: Hypophostasia. NCBI. PMID 20301329. Archived from the ... hypophosphatasia (for which it is often misdiagnosed), glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, ...
Retrieved 10 September 2014.{{cite web}}: CS1 maint: multiple names: authors list (link) "Hypophosphatasia Pathology". ... Hypophosphatasia.com. Retrieved 10 September 2014. Geelhoed, GW; Kelly, TR (December 1989). "Pseudogout as a clue and ... in cartilage Decreased levels of cartilage glycosaminoglycans Hyperparathyroidism Hemochromatosis Hypophosphatasia ...
"Hypophosphatasia: Signs and Symptoms". Hypophosphatasia.com. Archived from the original on 15 October 2014. Retrieved 10 ... like hypophosphatasia or hypophosphatemia, can also lead to rickets. Strontium is allied with calcium uptake into bones; at ...
TBCE Hypophosphatasia, adult; 146300; ALPL Hypophosphatasia, childhood; 241510; ALPL Hypophosphatasia, infantile; 241500; ALPL ...
"Childhood hypophosphatasia (Concept Id: C0220743) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-07-02. "Chromosome ... "Infantile hypophosphatasia (Concept Id: C0268412)". www.ncbi.nlm.nih.gov. Retrieved 2023-07-02. "Intellectual developmental ...
It is used to treat hypophosphatasia, a rare metabolic disorder. In 2016, the company became a member of the Pharmaceutical ... used to treat hypophosphatasia; sebelipase alfa (Kanuma), used to treat lysosomal acid lipase deficiency, and andexanet alfa ( ... and Juvenile-Onset Hypophosphatasia (HPP)" (Press release). Business Wire. October 23, 2015. Helfand, Carly (July 18, 2016). " ... a drug used to treat the genetic disorder hypophosphatasia, for as much as $1.08 billion. In June 2015, Alexion acquired ...
This enzyme has been linked directly to a disorder known as hypophosphatasia, a disorder that is characterized by low serum ALP ... Mornet E (2000). "Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene". Human Mutation. 15 (4 ... GeneReviews/NCBI/NIH/UW entry on Hypophosphatasia Human ALPL genome location and ALPL gene details page in the UCSC Genome ... Orimo H, Goseki-Sone M, Sato S, Shimada T (June 1997). "Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP ...
People with hypophosphatasia cannot make enough working ALP, which leads to weak bones. Asfotase alfa is a version of the human ... Hypophosphatasia is caused by a genetic defect of tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme that plays a role ... Bowden SA, Foster BL (2018). "Profile of asfotase alfa in the treatment of hypophosphatasia: design, development, and place in ... Scott LJ (February 2016). "Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia". Drugs. 76 (2): 255-62. doi:10.1007/ ...
... and pathological features of hypophosphatasia; based on the study of a family". The Quarterly Journal of Medicine. 25 (100): ...
... phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism". Journal of Clinical Investigation. ... tests are performed to rule out other causes and to confirm an elevated level of vitamin B6 with an absence of hypophosphatasia ...
"A Case of Spondylodysplastic Ehlers-Danlos Syndrome With Comorbid Hypophosphatasia". AACE Clinical Case Reports. 8 (6): 255-258 ...
It will be used to treat hypophosphatasia, a rare metabolic disorder. In 2015 Alexion estimated that Synageva, its specialty ...
Rockman-Greenberg is the leading Canadian researcher in the treatment of hypophosphatasia. She also developed targeted DNA- ...
It is a feature of conditions such as cleidocranial dysplasia and hypophosphatasia. Ireland R (25 March 2010). A Dictionary of ...
In contrast, low levels of ALP is found in hypothyroidism, pernicious anemia, zinc deficiency, and hypophosphatasia. ALP ...
... and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102-122. doi:10.1111/prd. ... the Stenciling Principle is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia and X- ...
... and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102-122. doi:10.1111/prd. ... Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia and X- ...
... and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102-22. doi:10.1111/prd.12029 ... Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia (HPP) ...
For both XLH and hypophosphatasia, inhibitor-enzyme pair relationships function to regulate mineralization in the extracellular ... and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102-22. doi:10.1111/prd.12029 ... and relationship to hypophosphatasia and X-linked hypophosphatemia". Periodontology 2000. 63 (1): 102-22. doi:10.1111/prd.12029 ...
... and hypophosphatasia. Looser zones are named after Emil Looser, a Swiss physician. A band of bone material of decreased density ...
April 2019). "Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in ... Hypophosphatasia, a genetic disorder Women receiving estrogen therapy for menopausal symptoms[citation needed] Estrogen- ...
... hypophosphatasia, geroderma osteodysplasticum, and Ehlers-Danlos syndrome.: 1513 : 253-256 Various forms of osteoporosis, such ...
Menke's syndrome Cleidocranial dysostosis Hypothyroidism and hypophosphatasia Otopalatodigital syndrome Primary acro-osteolysis ...
Achondrogenesis Atelosteogenesis III Boomerang dysplasia Campomelic dysplasia Ellis-Van Creveld syndrome Hypophosphatasia ...
... hyperprolinaemia type II and hypophosphatasia) can trigger vitamin B6 deficiency-dependent epileptic seizures in infants. These ...
... a muscle disease Hypophosphatasia, a bone disease Hypoxia preconditioned plasma Hardy-Pomeau-Pazzis model, in computational ...
... hypophosphatasia, and others. Necrotizing periodontal diseases are non-contagious infections but may occasionally occur in ...
... hypophosphatasia MeSH C18.452.648.618.544 - hypophosphatemia, familial MeSH C18.452.648.618.590 - Menkes kinky hair syndrome ...
Hypophosphatasia is considered particularly rare in people of African ancestry in the U.S. Hypophosphatasia is often discovered ... "Hypophosphatasia Signs and Symptoms". Hypophosphatasia.com. Archived from the original on 15 October 2014. Retrieved 10 ... "Hypophosphatasia". Genetics Home Reference. "Hypophosphatasia". NORD (National Organization for Rare Disorders). Retrieved 2020 ... but not adult hypophosphatasia. Perinatal hypophosphatasia is the most lethal form. Profound hypomineralization results in ...
... hypophosphatasia is a rare inborn error of metabolism caused by mutations in the gene encoding tissue-nonspecific isoenzyme of ... encoded search term (Hypophosphatasia (HPP)) and Hypophosphatasia (HPP) What to Read Next on Medscape ... Hypophosphatasia (HPP). Updated: Jun 05, 2023 * Author: Ricardo R Correa Marquez, MD, EsD, FACP, FACE, FAPCR, CMQ, ABDA, FACHT ... The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy ...
Asfotase alfa for treating paediatric-onset hypophosphatasia *Highly specialised technologies guidance. *Reference number: ... Evidence-based recommendations on asfotase alfa (Strensiq) for treating paediatric-onset hypophosphatasia in babies, children, ... and replaces NICE highly specialised technologies guidance HST6 on asfotase alfa for treating paediatric-onset hypophosphatasia ...
Treatments for Hypophosphatasia. Osteologie, 29 (4). S. 275 - 283. STUTTGART: GEORG THIEME VERLAG KG. ISSN 2567-5818 ... Hypophosphatasia due to genetically determined deficient activity of the tissue non-specific alkaline phosphatase (TNAP) is ...
How much do you know about juvenile hypophosphatasia? Test your knowledge with this quick quiz. ... Hypophosphatasia (HPP) is a rare inherited disease caused by mutations in the ALPL gene. The ALPL gene is responsible for the ...
Alkaline phosphatase, Asfotase alfa, Bone, Encephalopathy, Enzyme replacement therapy, Hypophosphatasia, Pyridoxine, Rare ... Lethal Encephalopathy in an Infant with Hypophosphatasia despite Enzyme Replacement Therapy Subject Area: Endocrinology , ... Adult Hypophosphatasia and a Low Level of Red Blood Cell Thiamine Pyrophosphate Ann Nutr Metab (May,2005) ... Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization- ...
Distribution of alkaline phosphatase in the serum proteins in hypophosphatasia Message subject: (Your Name) has forwarded a ...
Tag: hypophosphatasia. Hypophosphatasia: An Inherited Disease That Affects the Bones and Teeth. Chad Deal, MD • Sabrina K. ... Read More about Hypophosphatasia: An Inherited Disease That Affects the Bones and Teeth. ...
Perinatal Hypophosphatasia: Read more about Symptoms, Diagnosis, Treatment, Complications, Causes and Prognosis. ... Perinatal hypophosphatasia is usually suggested on antenatal ultrasonography with undermineralization of the long bones, skull ... Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: results from a Japanese clinical trial. ... Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary ...
... hypophosphatasia, McCune-Albright syndrome, and osteogenesis imperfecta with mineralization defect (syndrome resembling ... Hypophosphatasia. This autosomal recessive condition, which results in low activity of the tissue-nonspecific isoenzyme of ... Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016 Jun 16. 1 (9):e85971. [QxMD MEDLINE Link]. ... The effects of bone marrow transplant in hypophosphatasia are transient, and bone lesions may recur 6 months after the ...
Hypophosphatasia. About 300 mutations in the ALPL gene have been identified in people with hypophosphatasia. Most of these ... Mornet E. Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. Hum Mutat. 2000;15(4):309-15. ... Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. Endocr Rev. 1994 Aug;15(4):439-61. doi: ... Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016 Apr;12(4):233-46. doi: ...
Mutations of the tissue non-specific alkaline phosphatase gene (TNAP) causing a non-lethal case of perinatal hypophosphatasia. ... Mutations of the tissue non-specific alkaline phosphatase gene (TNAP) causing a non-lethal case of perinatal hypophosphatasia. ... Adolescent, Alkaline Phosphatase, Base Sequence, Female, Humans, Hypophosphatasia, Molecular Sequence Data, Mutation, Pedigree ...
... of amplitude-integrated electroencephalogram recordings and serum vitamin B6 metabolites in perinatal lethal hypophosphatasia ... An Interesting article from Japan on the utilisation of aEEG in Hypophosphatasia. This case showed that aEEG monitoring was ... of amplitude-integrated electroencephalogram recordings and serum vitamin B6 metabolites in perinatal lethal hypophosphatasia ...
Congenital Hypophosphatasia - Etiology, pathophysiology, symptoms, signs, diagnosis & prognosis from the MSD Manuals - Medical ... Congenital hypophosphatasia is absence or low levels of serum alkaline phosphatase due to mutations in the gene encoding tissue ... can be given by subcutaneous injection for treatment of congenital hypophosphatasia. Dosing is 2 mg/kg 3 times a week or 1 mg/ ...
... excepting the extremely rare benign perinatal hypophosphatasia. Childhood hypophosphatasia, defined as onset of symptoms ... Subsequent research has also shown improvements in morbidity for patients with childhood hypophosphatasia as measured by ... Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline ... which has shown significant improvements in morbidity and mortality in patients with perinatal and infantile hypophosphatasia. ...
Get to know some of the common misdiagnoses of hypophosphatasia (HPP). ... What are some common misdiagnoses and diseases that can look like hypophosphatasia (HPP)?. Several conditions share symptoms ... What are some common misdiagnoses and diseases that can look like hypophosphatasia (HPP)? ... What types of medications could be harmful for someone with hypophosphatasia (HPP)? ...
Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology. To read more please click on the ... Clinical and biochemical characteristics of adults with hypophosphatasia attending a metabolic bone clinic. To read more please ... The US Hypophosphatasia Foundation. 141 Hawkins Place, #267. Boonton, NJ 07005, USA. ...
5 Ways to Manage Symptoms of Hypophosphatasia. Hypophosphatasia can cause bone fractures, bone pain, and abnormal development ...
Osteoporosis, a chronic, progressive disease of multifactorial etiology (see Etiology), is the most common metabolic bone disease in the United States. It has been most frequently recognized in elderly white women, although it does occur in both sexes, all races, and all age groups.
Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. Low ALP is a screening tool for ... A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients.. en_US. ...
It is concluded that there is good evidence to associate hypophosphatasia, hypomagnesemia, and hyperparathyroidism with ...
Familial Hypophosphatasia;. Gorhams Vanishing Bone Disease;. Madura Foot;. Metaphyseal Dysplasia Diagnostic Problem;. Osseous ...
In the spring of 2020, I was officially diagnosed with Hypophosphatasia through genetic testing. In retrospect, the signs and ... Investigation of ALPL variant states and clinical outcomes: An analysis of adults and adolescents with hypophosphatasia treated ... The US Hypophosphatasia Foundation. 141 Hawkins Place, #267. Boonton, NJ 07005, USA. ... Dissecting Mutational Allosteric Effects in Alkaline Phosphatases Associated with Different Hypophosphatasia Phenotypes: An ...
Hypophosphatasia (polyhydramnios, short, deformed limbs, soft skull). ✓. ✓. Kenny-Caffey syndrome (hypoparathyroidism, dwarfism ... The condition can be idiopathic or caused by hyperthyroidism, hypophosphatasia, rickets, or hyperparathyroidism.20 It is also ...
1. Differential diagnosis of perinatal hypophosphatasia: radiologic perspectives. Amaka C. Offiah, Jerry Vockley, Craig F. ...
Hypophosphatasia and the Extracellular Metabolism of Inorganic Pyrophosphate: Clinical and Laboratory Aspects ... Hypophosphatasia and the Extracellular Metabolism of Inorganic Pyrophosphate: Clinical and Laboratory Aspects ...
... bone condition called hypophosphatasia experienced bone healing after use of an experimental therapy. ... But two weeks later, Evie began to have seizures, and a genetic test revealed she had hypophosphatasia, a rare metabolic ... In every case known at the time Evie was born, infants with hypophosphatasia and seizures had died within 18 months, Elsaesser ... There is no approved medical treatment for hypophosphatasia, but, thanks to a new experimental therapy, the outlook may change. ...
Ex vivo Engineering of Autologous Hematopoietic Stem Cells for the Treatment of Hypophosphatasia. Therapeutic Candidate or ... patients with hypophosphatasia and genetically modified with a lentiviral vector to release TNALP Indication Hypophosphatasia ( ...
Whyte, M. P. Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat. Rev. Endocrinol. 12, 233-246 ( ...
  • In radiographic examinations, perinatal hypophosphatasia can be distinguished from even the most severe forms of osteogenesis imperfecta and congenital dwarfism. (wikipedia.org)
  • The genetic mutations found in this case were previously reported in perinatal, infantile and childhood hypophosphatasia, but not adult hypophosphatasia. (wikipedia.org)
  • Compound heterozygosity and autosomal dominant mutations in the TNSALP gene may cause childhood and adult hypophosphatasia. (medscape.com)
  • citation needed] Infantile hypophosphatasia presents in the first 6 months of life, with the onset of poor feeding and inadequate weight gain. (wikipedia.org)
  • Another condition, pseudohypophosphatasia, is clinically indistinguishable from infantile hypophosphatasia, but serum alkaline phosphatase (ALP) activity is normal. (medscape.com)
  • Asfotase alfa (Strensiqâ„¢), is a first-in-class bone-targeted recombinant tissue nonspecific alkaline phosphatase which has shown significant improvements in morbidity and mortality in patients with perinatal and infantile hypophosphatasia. (biomedcentral.com)
  • Strensiq and Kanuma are injected enzyme replacement therapies that treat hypophosphatasia and lysosomal acid lipase deficiency, respectively. (pharmacytimes.com)
  • Findings of amplitude-integrated electroencephalogram recordings and serum vitamin B6 metabolites in perinatal lethal hypophosphatasia during enzyme replacement therapy. (neonatalcareacademy.com)
  • Patients with hypophosphatasia have low alkaline phosphatase activity levels, which leads to increased PPi, an inhibitor of hydroxyapatite crystal formation. (medscape.com)
  • Large-scale in vitro functional testing and novel variant scoring via protein modeling provide insights into alkaline phosphatase activity in hypophosphatasia. (bvsalud.org)
  • Hypophosphatasia due to genetically determined deficient activity of the tissue non-specific alkaline phosphatase (TNAP) is characterized by a wide spectrum of potential clinical manifestations, both, regarding the type of symptoms, as well as the severity of associated deficits. (uni-koeln.de)
  • Brun-Heath I, Taillandier A, Serre JL, Mornet E. Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations. (medlineplus.gov)
  • Mutations of the tissue non-specific alkaline phosphatase gene (TNAP) causing a non-lethal case of perinatal hypophosphatasia. (ox.ac.uk)
  • Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline phosphatase enzyme. (biomedcentral.com)
  • Subsequent research has also shown improvements in morbidity for patients with childhood hypophosphatasia as measured by improvement in rickets, growth, strength, mobility, and quality of life. (biomedcentral.com)
  • Low levels are associated with hyperthyroidism, and with the rare condition of idiopathic hypophosphatasia associated with rickets and the excretion of excess phosphatidyl ethanolamine in the urine. (cdc.gov)
  • Congenital hypophosphatasia is absence or low levels of serum alkaline phosphatase due to mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). (msdmanuals.com)
  • A low serum alkaline phosphatase may signal hypophosphatasia in osteoporosis clinic patients. (austin.org.au)
  • Hypophosphatasia (HPP) is a rare inherited disease caused by mutations in the ALPL gene. (medscape.com)
  • About 300 mutations in the ALPL gene have been identified in people with hypophosphatasia. (medlineplus.gov)
  • ALPL mutations that almost completely eliminate the activity of TNSALP usually result in the more severe forms of hypophosphatasia. (medlineplus.gov)
  • Hypophosphatasia (HPP) is a uncommon hereditary systemic illness that's characterised by faulty bone and/or dental mineralization, and is brought on by mutations within the alkaline phosphatase gene (ALPL). (stjosephs-hospital.com)
  • In the spring of 2020, I was officially diagnosed with Hypophosphatasia through genetic testing. (softbones.org)
  • The clinical presentation of hypophosphatasia varies from devastating prenatal intrauterine disease to mild manifestations in adulthood. (medscape.com)
  • Evidence-based recommendations on asfotase alfa (Strensiq) for treating paediatric-onset hypophosphatasia in babies, children, young people and adults. (nice.org.uk)
  • This guidance updates and replaces NICE highly specialised technologies guidance HST6 on asfotase alfa for treating paediatric-onset hypophosphatasia. (nice.org.uk)
  • Asfotase alfa , a recombinant protein carrying the catalytic domain of tissue-nonspecific alkaline phosphatase, can be given by subcutaneous injection for treatment of congenital hypophosphatasia. (msdmanuals.com)
  • When she was 2 months old, Evie was given a drug called asfotase alfa, an engineered protein designed to take the place of an enzyme that does not work properly in hypophosphatasia patients. (livescience.com)
  • Should I seek genetic testing for hypophosphatasia (HPP)? (hypophosphatasia.com)
  • But two weeks later, Evie began to have seizures, and a genetic test revealed she had hypophosphatasia , a rare metabolic condition that prevents minerals such as calcium and phosphorus from being properly deposited in bones. (livescience.com)
  • Perinatal hypophosphatasia is the most lethal form. (wikipedia.org)
  • Radiographic features in infants are generally less severe than those seen in perinatal hypophosphatasia. (wikipedia.org)
  • In one study, 19% of patients diagnosed with fibromyalgia had laboratory findings suggestive of possible hypophosphatasia. (wikipedia.org)
  • Hypophosphatasia was diagnosed in 3% of osteoporosis clinic patients with low ALP. (austin.org.au)
  • Future work will be needed to see if the drug can completely reverse the condition if started as soon as it is diagnosed, said Rimoin, who with his colleagues is collecting information on hypophosphatasia patients to better understand the natural course of the disease. (livescience.com)
  • On this episode of CoRDS Cast, Alyssa and Polly sit down with Deborah Fowler who is the President and Founder of Soft Bones, Inc. Hypophosphatasia or HPP is a metabolic bone condition that most often affects the development of bones and teeth. (spotify.com)
  • Estimates for less severe forms of hypophosphatasia have been made utilizing molecular data and have suggested an incidence of 1 in 6370 [ 4 ]. (biomedcentral.com)
  • In the study, which included 11 infants and children with severe hypophosphatasia, the drug healed bones, reduced deformities of the skeleton and improved children's strength and breathing abilities. (livescience.com)
  • Fast Five Quiz: Juvenile Hypophosphatasia Management - Medscape - Jul 22, 2022. (medscape.com)
  • Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization-associated alkaline phosphatase gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). (karger.com)
  • Mornet E. Hypophosphatasia: the mutations in the tissue-nonspecific alkaline phosphatase gene. (medlineplus.gov)
  • What are some common misdiagnoses and diseases that can look like hypophosphatasia (HPP)? (hypophosphatasia.com)
  • Researchers believe that a buildup of one of these compounds, inorganic pyrophosphate, underlies the defective mineralization of bones and teeth in people with hypophosphatasia. (medlineplus.gov)
  • Evie Elsaesser (left) has a rare bone condition called hypophosphatasia, and has received an experimental treatment for the disease since she was 2 months old. (livescience.com)
  • Hypophosphatasia and the role of alkaline phosphatase in skeletal mineralization. (medlineplus.gov)
  • Low ALP is a screening tool for hypophosphatasia, a condition potentially aggravated by antiresorptive therapy. (austin.org.au)
  • Deborah's son was diagnosed with Hypophosphatasia at 18 months old and she is a strong advocate for this rare condition. (spotify.com)
  • There is no approved medical treatment for hypophosphatasia, but, thanks to a new experimental therapy, the outlook may change. (livescience.com)
  • The disease is life-threatening when manifesting within the first six months of life, excepting the extremely rare benign perinatal hypophosphatasia. (biomedcentral.com)
  • In every case known at the time Evie was born, infants with hypophosphatasia and seizures had died within 18 months, Elsaesser said. (livescience.com)
  • Hypophosphatasia (HPP) is a multisystem disease with deleterious effects that can appear at different ages and progress over time. (medscape.com)
  • She's running with hypophosphatasia to show her daughter how to be strong. (womensrunning.com)