Autosomal recessive disorder caused by mutations in the mevalonate kinase gene. Because of the mutations cholesterol biosynthesis is disrupted and MEVALONIC ACID accumulates. It is characterized by a range of symptoms, including dysmorphic FACIES, psychomotor retardation, CATARACT, hepatosplenomegaly, CEREBELLAR ATAXIA, elevated IMMUNOGLOBULIN D, and recurrent febrile crises with FEVER; LYMPHADENOPATHY; ARTHRALGIA; EDEMA; and rash.
A condition marked by progressive CEREBELLAR ATAXIA combined with MYOCLONUS usually presenting in the third decade of life or later. Additional clinical features may include generalized and focal SEIZURES, spasticity, and DYSKINESIAS. Autosomal recessive and autosomal dominant patterns of inheritance have been reported. Pathologically, the dentate nucleus and brachium conjunctivum of the CEREBELLUM are atrophic, with variable involvement of the spinal cord, cerebellar cortex, and basal ganglia. (From Joynt, Clinical Neurology, 1991, Ch37, pp60-1)
Mevalonic acid is a crucial intermediate compound in the HMG-CoA reductase pathway, which is a metabolic route that produces cholesterol, other steroids, and isoprenoids in cells.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
Any one of a group of congenital hemolytic anemias in which there is no abnormal hemoglobin or spherocytosis and in which there is a defect of glycolysis in the erythrocyte. Common causes include deficiencies in GLUCOSE-6-PHOSPHATE ISOMERASE; PYRUVATE KINASE; and GLUCOSE-6-PHOSPHATE DEHYDROGENASE.
Hereditary disorders of pyruvate metabolism. They are difficult to diagnose and describe because pyruvate is a key intermediate in glycolysis, gluconeogenesis, and the tricarboxylic acid cycle. Some inherited metabolic disorders may alter pyruvate metabolism indirectly. Disorders in pyruvate metabolism appear to lead to deficiencies in neurotransmitter synthesis and, consequently, to nervous system disorders.
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
Hemolytic anemia due to various intrinsic defects of the erythrocyte.
A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement.
Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.
Inborn errors of carbohydrate metabolism are genetic disorders that result from enzyme deficiencies or transport defects in the metabolic pathways responsible for breaking down and processing carbohydrates, leading to accumulation of toxic intermediates or energy deficits, and typically presenting with multisystem clinical manifestations.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.
An enzyme that catalyzes the conversion of ATP and PHOSPHORYLASE B to ADP and PHOSPHORYLASE A.
An excess of GAMMA-GLOBULINS in the serum due to chronic infections or PARAPROTEINEMIAS.
A group of HEREDITARY AUTOINFLAMMATION DISEASES, characterized by recurrent fever, abdominal pain, headache, rash, PLEURISY; and ARTHRITIS. ORCHITIS; benign MENINGITIS; and AMYLOIDOSIS may also occur. Homozygous or compound heterozygous mutations in marenostrin gene result in autosomal recessive transmission; simple heterozygous, autosomal dominant form of the disease.

Hereditary periodic fever syndromes. (1/28)

The hereditary periodic fevers are a group of Mendelian disorders characterized by seemingly unprovoked fever and localized inflammation. Recent data indicate that these illnesses represent inborn errors in the regulation of innate immunity. Pyrin, the protein mutated in familial Mediterranean fever, defines an N-terminal domain found in a large family of proteins involved in inflammation and apoptosis. Through this domain pyrin may play a role in the regulation of interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and leukocyte apoptosis. Cryopyrin/NALP3, another protein in this family, is mutated in three other hereditary febrile syndromes and participates in the inflammasome, a newly recognized macromolecular complex crucial to IL-1beta activation. Somewhat unexpectedly, mutations in the 55 kDa receptor for tumor necrosis factor also give rise to a dominantly inherited periodic fever syndrome, rather than immunodeficiency, a finding that has stimulated important investigations into both pathogenesis and treatment. Finally, the discovery of the genetic basis of the hyperimmunoglobulinemia D with periodic fever syndrome suggests an as yet incompletely understood connection between the mevalonate pathway and the regulation of cytokine production. These insights extend our understanding of the regulation of innate immunity in man, while providing the conceptual basis for the rational design of targeted therapies, both for the hereditary periodic fevers themselves and other inflammatory disorders as well.  (+info)

Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. (2/28)

OBJECTIVE: The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was originally defined by the presence of a high serum level of immunoglobulin D associated with recurrent fever. Since the discovery of the mevalonate kinase gene (MVK) gene encoding the mevalonate kinase enzyme, most patients with a clinical diagnostic of HIDS are now found to have a mevalonate kinase deficiency based on metabolic and genetic data. We aimed to asses the value of a high IgD serum level for the diagnosis of HIDS in a cohort of patients with a phenotype of recurrent fever, and to characterize patients with a high IgD serum level without mevalonate kinase mutation. METHODS: Main clinical and biological data of 50 patients who presented with clinical signs compatible with HIDS have been prospectively registered on a standard form. Clinical data have been analysed according the IgD serum level and the presence of MVK mutation. RESULTS: The metabolic and genetic data establishing the diagnosis of HIDS correlated in all cases. In this series of 50 patients, the sensitivity of a high IgD value for the diagnosis of HIDS is 0.79. In five patients with MVK mutation, IgD levels were found to be in the normal range. Likelihood ratios indicate that IgD measurement is not relevant for the diagnostic of HIDS. Most patients with a high serum IgD level and no MVK mutation have no definite diagnosis. CONCLUSION: The clinical relevance of the IgD measurement for the diagnosis of MKD in our population appears as poor, as reflected by likelihood ratios which are both close to 1.  (+info)

Autoinflammatory diseases: an update of clinical and genetic aspects. (3/28)

 (+info)

HMG-CoA reductase inhibition induces IL-1beta release through Rac1/PI3K/PKB-dependent caspase-1 activation. (4/28)

 (+info)

Abnormal IgD and IgA1 O-glycosylation in hyperimmunoglobulinaemia D and periodic fever syndrome. (5/28)

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Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. (6/28)

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Children's toxicology from bench to bed--Liver Injury (4): Mitochondrial respiratory chain disorder and liver disease in children. (7/28)

OBJECTIVES: The present study was aimed to ascertain the contributions of mitochondrial respiratory chain (MRC) enzymes to the development of liver failure and to the liver pathophysiology of metabolic liver diseases. METHODS: We investigated liver samples obtained from 8 patients with liver failure due to unknown etiology and from 15 patients with metabolic disease: ornithine transcarbamylase deficiency, 6 cases; Wilson disease, 3 cases; metylmalonic aciduria (MMA); 3 cases, neonatal hemochromatosis, 2 cases. The estimation of MRC enzymes was carried out by the following independent methods; i) blue native polyacrylamide gel electrophoresis (BN-PAGE) in gel enzyme staining, ii) BN-PAGE western blotting, iii) in vitro MRC enzyme assay. Furthermore, we estimated the quantities of mtDNA and nDNA using qPCR. RESULT: 4 cases with liver failure showed low activities and protein levels of complex I, III and IV. We also performed qPCR and estimated the ratio mtDNA/nDNA using these samples. They all exhibited extremely low ratio. They were diagnosed as mtDNA depletion syndrome. All cases except MMA cases exhibited mildly or moderately suppressed activities of complex I-IV. However, the respective protein levels remained almost normal. MMA cases exhibited low activities and protein levels of complex I, III and IV. In particular, their low activities and protein levels of complex I were noticeable. They all exhibited normal ratios of mtDNA to nDNA. CONCLUSION: MRC defect might be an etiology of liver failure in a considerable number of patients in Japan. The present study suggested that considerable disturbance of MRC occurs in children with metabolic diseases and possibly modifies the pathophysiology.  (+info)

The inherited autoinflammatory syndrome: a decade of discovery. (8/28)

The hereditary autoinflammatory diseases arise from mutations of genes regulating the innate immune system. These rare disorders are well characterized, both clinically and in terms of their molecular pathogenesis. The recurrent attacks of febrile polyserositis of Familial Mediterranean Fever (FMF) are due to defective pyrin, a protein that down-regulates inflammation. The Hyperimmunoglobulinemia D Syndrome (HIDS), which mimics FMF, results from a genetically conferred deficiency of mevalonate kinase. TRAPS (TNF Receptor Associated Periodic Syndrome), formerly known as Familial Hibernian Fever, is caused by a defective membrane receptor for TNF. Three other hereditary disorders which overlap in their clinical expression - Familial Cold Autoinflammatory Syndrome, the Muckle Wells syndrome, and Neonatal Onset Multisystem Inflamatory Disease (NOMID) - are a consequence of gain-of-function mutations of the gene encoding cryopyrin, the scaffolding protein of the inflammasome. The PAPA syndrome (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) results from mutations of a gene that increases the binding of its product (PSPSTPIP1) to pyrin, thereby blunting the inhibitory effect of pyrin on inflammasome activation.  (+info)

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive genetic disorder that affects the metabolism of cholesterol and other essential isoprenoids. It is caused by mutations in the MVK gene, which provides instructions for making the enzyme mevalonate kinase.

This enzyme plays a critical role in the production of isoprenoids, including cholesterol, coenzyme Q10, and dolichols, which are essential for various cellular functions such as membrane stability, protein prenylation, and glycosylation. In MKD, the deficiency of mevalonate kinase leads to an accumulation of its substrate, mevalonic acid, and a decrease in isoprenoid production.

MKD has two clinical manifestations: hyperimmunoglobulin D syndrome (HIDS) and mevalonic aciduria (MA). HIDS is the milder form of the disorder, characterized by recurrent fever episodes, gastrointestinal symptoms, rash, lymphadenopathy, and joint pain. MA is the severe form of MKD, which presents with developmental delay, neurological impairment, cataracts, failure to thrive, and recurrent infections. Both forms of MKD are associated with increased levels of mevalonic acid in body fluids, including urine and blood.

The diagnosis of MKD is based on clinical features, biochemical markers, and genetic testing. Treatment options for MKD include anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and biologic agents such as anakinra and canakinumab, which target the interleukin-1 (IL-1) pathway. In some cases, dietary modifications and supplementation with coenzyme Q10 may also be beneficial.

Myoclonic cerebellar dyssynergia is not a widely recognized or formally defined medical term. However, based on its individual components, it can be inferred to refer to a neurological condition characterized by:

1. Myoclonus: These are sudden, involuntary jerking movements of a muscle or group of muscles. They typically occur as a result of hyperexcitability of the neurons in the brain that control movement (motor neurons).
2. Cerebellar: The cerebellum is a part of the brain responsible for coordinating muscle movements, maintaining posture and balance, and fine-tuning motor skills. When a condition is described as "cerebellar," it implies that there is some dysfunction or abnormality in this region of the brain.
3. Dyssynergia: This term refers to a lack of coordination between muscles and muscle groups during voluntary movements. It can result from damage to the cerebellum or other parts of the nervous system involved in motor control.

Therefore, myoclonic cerebellar dyssynergia could be interpreted as a condition characterized by involuntary muscle jerks (myoclonus) and impaired coordination of voluntary movements (dyssynergia), likely due to cerebellar dysfunction. However, it is essential to consult with a medical professional for an accurate diagnosis and treatment plan if you or someone else experiences symptoms that may align with this description.

Mevalonic acid is not a term that is typically used in medical definitions, but rather it is a biochemical concept. Mevalonic acid is a key intermediate in the biosynthetic pathway for cholesterol and other isoprenoids. It is formed from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) by the enzyme HMG-CoA reductase, which is the target of cholesterol-lowering drugs known as statins.

In a medical context, mevalonic acid may be mentioned in relation to certain rare genetic disorders, such as mevalonate kinase deficiency (MKD) or hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), which are caused by mutations in the gene encoding mevalonate kinase, an enzyme involved in the metabolism of mevalonic acid. These conditions can cause recurrent fevers, rashes, joint pain, and other symptoms.

Glycerol kinase is an enzyme that plays a crucial role in the metabolism of glycerol, which is a simple carbohydrate. The enzyme catalyzes the conversion of glycerol to glycerol-3-phosphate by transferring a phosphate group from ATP to glycerol. This reaction is an essential step in the metabolic pathway that leads to the formation of glucose or other energy-rich compounds in the body.

There are two main forms of glycerol kinase found in humans, designated as GK1 and GK2. GK1 is primarily expressed in the liver, while GK2 is found in various tissues, including the brain, heart, and muscles. Deficiencies in glycerol kinase can lead to metabolic disorders such as hyperglycerolemia, which is characterized by high levels of glycerol in the blood.

Pyruvate kinase is an enzyme that plays a crucial role in the final step of glycolysis, a process by which glucose is broken down to produce energy in the form of ATP (adenosine triphosphate). Specifically, pyruvate kinase catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), resulting in the formation of pyruvate and ATP.

There are several isoforms of pyruvate kinase found in different tissues, including the liver, muscle, and brain. The type found in red blood cells is known as PK-RBC or PK-M2. Deficiencies in pyruvate kinase can lead to a genetic disorder called pyruvate kinase deficiency, which can result in hemolytic anemia due to the premature destruction of red blood cells.

Hemolytic anemia, congenital nonspherocytic is a rare type of inherited anemia characterized by the premature destruction (hemolysis) of red blood cells. This condition is caused by defects in enzymes or proteins that help maintain the structural integrity and function of red blood cells.

In this form of hemolytic anemia, the red blood cells are not spherical in shape like spherocytes; instead, they may be oval or elongated. The most common types of congenital nonspherocytic hemolytic anemia are caused by deficiencies in enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase.

Symptoms of this condition may include fatigue, weakness, pale skin, jaundice, dark urine, and an enlarged spleen. Treatment may involve blood transfusions, medications to manage symptoms, and avoidance of certain triggers that can exacerbate the hemolysis. In some cases, a bone marrow transplant may be considered as a curative treatment option.

Inborn errors of pyruvate metabolism refer to genetic disorders that affect the body's ability to properly metabolize pyruvate, a key intermediate in glucose metabolism. Pyruvate is produced in the cells during the breakdown of glucose for energy production. Normally, pyruvate can be converted into acetyl-CoA and enter the citric acid cycle (also known as the Krebs cycle) for further energy production. However, in individuals with inborn errors of pyruvate metabolism, this conversion process is impaired due to defects in enzymes or transport proteins involved in pyruvate metabolism.

There are several types of inborn errors of pyruvate metabolism, including:

1. Pyruvate dehydrogenase deficiency: This is a genetic disorder caused by mutations in the genes encoding components of the pyruvate dehydrogenase (PDH) complex, which catalyzes the conversion of pyruvate to acetyl-CoA. PDH deficiency can lead to lactic acidosis, neurological problems, and developmental delay.
2. Pyruvate carboxylase deficiency: This is a rare genetic disorder caused by mutations in the gene encoding pyruvate carboxylase, an enzyme that converts pyruvate to oxaloacetate, which can then be used to synthesize glucose. Pyruvate carboxylase deficiency can cause lactic acidosis, seizures, and developmental delay.
3. Mitochondrial disorders: Some mitochondrial disorders can affect pyruvate metabolism by impairing the function of the electron transport chain, which is necessary for energy production in the cells. These disorders can lead to lactic acidosis, muscle weakness, and neurological problems.
4. Other inborn errors: There are several other rare genetic disorders that can affect pyruvate metabolism, including defects in the mitochondrial pyruvate carrier protein, which transports pyruvate into the mitochondria, and deficiencies in enzymes involved in the citric acid cycle.

Treatment for these disorders typically involves managing symptoms, such as controlling lactic acidosis and providing supportive care for neurological problems. In some cases, dietary modifications or supplements may be recommended to help improve pyruvate metabolism.

Hemolytic anemia is a type of anemia that occurs when red blood cells are destroyed (hemolysis) faster than they can be produced. Red blood cells are essential for carrying oxygen throughout the body. When they are destroyed, hemoglobin and other cellular components are released into the bloodstream, which can lead to complications such as kidney damage and gallstones.

Hemolytic anemia can be inherited or acquired. Inherited forms of the condition may result from genetic defects that affect the structure or function of red blood cells. Acquired forms of hemolytic anemia can be caused by various factors, including infections, medications, autoimmune disorders, and certain medical conditions such as cancer or blood disorders.

Symptoms of hemolytic anemia may include fatigue, weakness, shortness of breath, pale skin, jaundice (yellowing of the skin and eyes), dark urine, and a rapid heartbeat. Treatment for hemolytic anemia depends on the underlying cause and may include medications, blood transfusions, or surgery.

Hemolytic anemia, congenital is a type of anemia that is present at birth and characterized by the abnormal breakdown (hemolysis) of red blood cells. This can occur due to various genetic defects that affect the structure or function of the red blood cells, making them more susceptible to damage and destruction.

There are several types of congenital hemolytic anemias, including:

1. Congenital spherocytosis: A condition caused by mutations in genes that affect the shape and stability of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
2. G6PD deficiency: A genetic disorder that affects the enzyme glucose-6-phosphate dehydrogenase (G6PD), which is essential for protecting red blood cells from damage. People with this condition have low levels of G6PD, making their red blood cells more susceptible to hemolysis when exposed to certain triggers such as infections or certain medications.
3. Hereditary elliptocytosis: A condition caused by mutations in genes that affect the structure and flexibility of red blood cells, leading to the formation of abnormally shaped and fragile cells that are prone to hemolysis.
4. Pyruvate kinase deficiency: A rare genetic disorder that affects an enzyme called pyruvate kinase, which is essential for the production of energy in red blood cells. People with this condition have low levels of pyruvate kinase, leading to the formation of fragile and abnormally shaped red blood cells that are prone to hemolysis.

Symptoms of congenital hemolytic anemia can vary depending on the severity of the condition but may include fatigue, weakness, pale skin, jaundice, dark urine, and an enlarged spleen. Treatment may involve blood transfusions, medications to manage symptoms, and in some cases, surgery to remove the spleen.

Glycogen storage disease (GSD) is a group of rare inherited metabolic disorders that affect the body's ability to break down and store glycogen, a complex carbohydrate that serves as the primary form of energy storage in the body. These diseases are caused by deficiencies or dysfunction in enzymes involved in the synthesis, degradation, or transport of glycogen within cells.

There are several types of GSDs, each with distinct clinical presentations and affected organs. The most common type is von Gierke disease (GSD I), which primarily affects the liver and kidneys. Other types include Pompe disease (GSD II), McArdle disease (GSD V), Cori disease (GSD III), Andersen disease (GSD IV), and others.

Symptoms of GSDs can vary widely depending on the specific type, but may include:

* Hypoglycemia (low blood sugar)
* Growth retardation
* Hepatomegaly (enlarged liver)
* Muscle weakness and cramping
* Cardiomyopathy (heart muscle disease)
* Respiratory distress
* Developmental delays

Treatment for GSDs typically involves dietary management, such as frequent feedings or a high-protein, low-carbohydrate diet. In some cases, enzyme replacement therapy may be used to manage symptoms. The prognosis for individuals with GSDs depends on the specific type and severity of the disorder.

Inborn errors of metabolism (IEM) refer to a group of genetic disorders caused by defects in enzymes or transporters that play a role in the body's metabolic processes. These disorders result in the accumulation or deficiency of specific chemicals within the body, which can lead to various clinical manifestations, such as developmental delay, intellectual disability, seizures, organ damage, and in some cases, death.

Examples of IEM include phenylketonuria (PKU), maple syrup urine disease (MSUD), galactosemia, and glycogen storage diseases, among many others. These disorders are typically inherited in an autosomal recessive manner, meaning that an affected individual has two copies of the mutated gene, one from each parent.

Early diagnosis and management of IEM are crucial to prevent or minimize complications and improve outcomes. Treatment options may include dietary modifications, supplementation with missing enzymes or cofactors, medication, and in some cases, stem cell transplantation or gene therapy.

Inborn errors of carbohydrate metabolism refer to genetic disorders that affect the body's ability to break down and process carbohydrates, which are sugars and starches that provide energy for the body. These disorders are caused by defects in enzymes or transport proteins that play a critical role in the metabolic pathways involved in carbohydrate metabolism.

There are several types of inborn errors of carbohydrate metabolism, including:

1. Galactosemia: This disorder affects the body's ability to metabolize the sugar galactose, which is found in milk and other dairy products. It is caused by a deficiency of the enzyme galactose-1-phosphate uridylyltransferase.
2. Glycogen storage diseases: These disorders affect the body's ability to store and break down glycogen, which is a complex carbohydrate that serves as a source of energy for the body. There are several types of glycogen storage diseases, each caused by a deficiency in a different enzyme involved in glycogen metabolism.
3. Hereditary fructose intolerance: This disorder affects the body's ability to metabolize the sugar fructose, which is found in fruits and sweeteners. It is caused by a deficiency of the enzyme aldolase B.
4. Pentose phosphate pathway disorders: These disorders affect the body's ability to metabolize certain sugars and generate energy through the pentose phosphate pathway. They are caused by defects in enzymes involved in this pathway.

Symptoms of inborn errors of carbohydrate metabolism can vary widely depending on the specific disorder and its severity. Treatment typically involves dietary restrictions, supplementation with necessary enzymes or cofactors, and management of complications. In some cases, enzyme replacement therapy or even organ transplantation may be considered.

Phosphotransferases are a group of enzymes that catalyze the transfer of a phosphate group from a donor molecule to an acceptor molecule. This reaction is essential for various cellular processes, including energy metabolism, signal transduction, and biosynthesis.

The systematic name for this group of enzymes is phosphotransferase, which is derived from the general reaction they catalyze: D-donor + A-acceptor = D-donor minus phosphate + A-phosphate. The donor molecule can be a variety of compounds, such as ATP or a phosphorylated protein, while the acceptor molecule is typically a compound that becomes phosphorylated during the reaction.

Phosphotransferases are classified into several subgroups based on the type of donor and acceptor molecules they act upon. For example, kinases are a subgroup of phosphotransferases that transfer a phosphate group from ATP to a protein or other organic compound. Phosphatases, another subgroup, remove phosphate groups from molecules by transferring them to water.

Overall, phosphotransferases play a critical role in regulating many cellular functions and are important targets for drug development in various diseases, including cancer and neurological disorders.

Phosphorylase Kinase (PhK) is a key enzyme in the regulation of glycogen metabolism, primarily involved in the breakdown of glycogen to glucose-1-phosphate. It is a serine/threonine protein kinase that catalyzes the phosphorylation of glycogen phosphorylase b, an isoform of glycogen phosphorylase, converting it into its active form, glycogen phosphorylase a.

PhK is composed of four different subunits: α, β, γ, and δ. The γ subunit contains the catalytic site, while the other subunits play regulatory roles. PhK itself can be activated by calcium ions (Ca2+) and protein kinase A (PKA)-mediated phosphorylation.

Phosphorylase Kinase is primarily located in the sarcoplasmic reticulum of muscle cells, where it plays a crucial role in regulating energy production during muscle contraction and relaxation. Dysregulation or mutations in PhK have been implicated in several genetic disorders, such as Debré-akaki syndrome, which is characterized by muscle weakness and cardiac abnormalities.

Hypergammaglobulinemia is a medical condition characterized by an elevated level of gamma globulins (a type of immunoglobulins or antibodies) in the blood. These proteins are part of the body's immune system and help to fight off infections. However, when their levels become too high, it can indicate an underlying medical disorder.

There are several types of hypergammaglobulinemia, including:

1. Primary hypergammaglobulinemia: This is a rare condition that is present at birth or develops during early childhood. It is caused by genetic mutations that lead to overproduction of immunoglobulins.
2. Secondary hypergammaglobulinemia: This type is more common and is caused by an underlying medical condition, such as chronic infections, autoimmune disorders, or certain types of cancer.

Symptoms of hypergammaglobulinemia can vary depending on the cause and severity of the condition. They may include recurrent infections, fatigue, swelling of the lymph nodes, and joint pain. Treatment typically involves addressing the underlying cause of the condition, if possible, as well as managing symptoms and preventing complications.

Familial Mediterranean Fever (FMF) is a hereditary inflammatory disorder that primarily affects people of Mediterranean ancestry, including populations from Turkey, Armenia, Arab countries, and Jewish communities from the Middle East. It is caused by mutations in the MEFV gene, which provides instructions for making a protein called pyrin or marenostrin.

The main features of FMF include recurrent episodes of fever, serositis (inflammation of the membranes lining the abdominal cavity, chest cavity, or heart), and polyserositis (inflammation affecting multiple serous membranes simultaneously). The attacks usually last between 12 and 72 hours and can be associated with severe abdominal pain, joint pain, and skin rashes.

The diagnosis of FMF is based on clinical criteria, family history, and genetic testing. Treatment typically involves the use of colchicine, an anti-inflammatory medication that helps prevent attacks and reduces the risk of long-term complications such as amyloidosis, a condition characterized by the buildup of abnormal protein deposits in various organs.

Early diagnosis and treatment of FMF are essential to prevent complications and improve quality of life for affected individuals.

"Mevalonate Kinase Deficiency". Mulders-Manders, CM; Simon, A (2015). "Hyper-IgD syndrome/mevalonate kinase deficiency: what is ... Mevalonate kinase deficiency is inherited in an autosomal recessive manner, meaning that a child must inherit a defective copy ... Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the ... Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol ...
Children with mevalonate kinase deficiency may remain undiagnosed for a long time as there is not enough scientific data at the ... Mevalonate kinase is an enzyme (specifically a kinase) that in humans is encoded by the MVK gene. Mevalonate kinases are found ... A reduction in mevalonate kinase activity to around 5-10% of its typical value is associated with the mevalonate kinase ... Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor ...
Hyperimmunoglobulin D syndrome in 50% of cases is associated with mevalonate kinase deficiency which can be measured in the ... Deficiency of the interleukin-1-receptor antagonist (DIRA) Familial cold urticaria, a similar disease List of cutaneous ...
One of the best-known pyrin AIDs is Mevalonate kinase deficiency, which is an enzyme in the cholesterol biosynthesis pathway. ... Episodic and multisystemic AIDs (NLRP12-associated disease, Mevalonate kinase deficiency, PFAPA (Periodic fever syndrome, ... Mevalonate kinase deficiency or Muckle-Wells syndrome) NFκB activation (NLRP12-associated disease, Crohn's disease or Blau ... The constitutive activation of NF-κB, not only in CD, is in particular caused by alanine (A20) deficiency. NFκB pathway is ...
... kinase Polyprenols Solagran Mevalonate inhibition#Dolichol Inhibition Fedorow, Heidi; Pickford, Russell; Hook, James M ... the medical significance of polyprenols and their substitution with dolichols when ingested where there is a deficiency. Trials ... Dolichol is a product of the HMG-CoA reductase pathway (also known as the mevalonate pathway), and as such their creation and ... availability are affected by mevalonate inhibition. First, a cis (or Z) -prenyltransferase (Dehydrodolichyl diphosphate ...
A number of diseases affect the mevalonate pathway: Mevalonate Kinase Deficiency Mevalonic Aciduria Hyperimmunoglobulinemia D ... The lower mevalonate pathway which converts (R)-mevalonate into IPP and DMAPP has 3 variants. In eukaryotes, mevalonate is ... Archaeal Mevalonate Pathway I). A third mevalonate pathway variant found in Thermoplasma acidophilum, phosphorylates mevalonate ... Statins inhibit HMG-CoA reductase within the mevalonate pathway. The mevalonate pathway of eukaryotes, archaea, and eubacteria ...
Hyper-IgD syndrome also known as Mevalonate kinase deficiency, and TNF receptor associated periodic syndrome (TRAPS), and a ... Anakinra was approved by the US Food and Drug Administration for the treatment of deficiency of the interleukin-1-receptor ...
ISO 3166-1 alpha-3 code and IOC country code Mevalonate kinase deficiency, a metabolic disorder mkd (software), a documentation ...
This particular classification encompasses both hereditary types (familial Mediterranean fever, mevalonate kinase deficiency, ...
... mevalonate kinase deficiency (MKD), and familial mediterranean fever (FMF). In June 2020, canakinumab was approved in the ... mevalonate kinase deficiency (MKD), familial Mediterranean fever (FMF), Still's disease, and gouty arthritis. In August 2023, ...
... mut-0 Methylmalonyl-Coenzyme A mutase deficiency Mevalonate kinase deficiency Mevalonicaciduria Meyenburg-Altherr-Uehlinger ... Multiple p Multiple acyl-CoA deficiency Multiple carboxylase deficiency, biotin responsive Multiple carboxylase deficiency, ... deficiency Methyl mercury antenatal infection Methylcobalamin deficiency cbl G type Methylcobalamin deficiency, cbl E ... and Becker type Muscular dystrophy Muscular fibrosis multifocal obstructed vessels Muscular phosphorylase kinase deficiency ...
Marc Delpech in Paris - that the syndrome was due to mutations of the gene encoding for mevalonate kinase, an enzyme in the ... October 2009). "Human dectin-1 deficiency and mucocutaneous fungal infections". The New England Journal of Medicine. 361 (18): ... June 1999). "Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper- ... has led to profound changes in the occurrence of TLR4 polymorphisms Deficiency of dectin-1 leads to increased susceptibility to ...
Mevalonate kinase deficiency) CIAS1-related diseases: Muckle-Wells syndrome Familial cold autoinflammatory syndrome, types 1, 2 ... deficiency MST1 deficiency TCRα deficiency LCK deficiency IL-21 deficiency IL-21R deficiency UNC119 deficiency NIK deficiency ... CD25 deficiency CD27 deficiency STAT5b deficiency ITK deficiency SH2D1A deficiency (XLP1) MAGT1 deficiency DOCK2 deficiency ... CD40 deficiency CD3γ deficiency CD8 deficiency ICOS deficiency ZAP70 deficiency Ca++ channel deficiency MHC class I deficiency ...
GHMP is an abbreviation referring to its original members: galactokinase, homoserine kinase, mevalonate kinase, and ... Galactokinase deficiency, also known as galactosemia type II, is a recessive metabolic disorder caused by a mutation in human ... Galactokinase does not belong to the sugar kinase family, but rather to a class of ATP-dependent enzymes known as the GHMP ... Hoffmeister D, Yang J, Liu L, Thorson JS (November 2003). "Creation of the first anomeric D/L-sugar kinase by means of directed ...
Monitoring liver enzymes and creatine kinase is especially prudent in those on high-dose statins or in those on statin/fibrate ... In people with homozygous deficiencies, statins may still prove helpful, albeit at high doses and in combination with other ... Statins act by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Because statins ... Sawada N, Liao JK (March 2014). "Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in ...
... homoserine kinase, mevalonate kinase, and phosphomevalonate kinase). Both mevalonate kinase and mevalonate diphosphate ... In humans, it is hypothesized that cholesterol deficiency may make the plasma membranes fragile and, as a result, induce ... Mevalonate diphosphate decarboxylase catalyzes the final step in the mevalonate pathway. The mevalonate pathway is responsible ... Scientists have classified mevalonate diphosphate decarboxylase as an enzyme in the GHMP kinase family (galactokinase, ...
During biotin deficiency, HMB can be synthesized from MC-CoA via enoyl-CoA hydratase and an unknown thioesterase enzyme, which ... the p70S6 kinase and the translation repressor protein 4EBP1). Supplementation with HMB in several non-human animal species has ... is then cleaved into acetyl-CoA and acetoacetate by HMG-CoA lyase or used in the production of cholesterol via the mevalonate ... a serine/threonine-specific protein kinase. The free acid (HMB-FA) and monohydrated calcium salt (HMB-Ca) forms of HMB have ...
This shows that the mevalonate pathway plays a role in controlling the expression of cytokines in microglia and may be ... Microglia interact with β-amyloid plaques through cell surface receptors that are linked to tyrosine kinase based signaling ... stated in 2006 that "using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, ... have shown that they are activated by diverse stimuli but they are dependent on activation of mitogen-activated protein kinase ...
It also includes multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites (regulatory ... The rate limiting step of cholesterol synthesis is the conversion of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonate, ... "The implications of 7-dehydrosterol-7-reductase deficiency (Smith-Lemli-Opitz syndrome) to neurosteroid production". Steroids. ... The translation (creating the enzyme from the mRNA transcript) of HMG-CoA reductase is inhibited by derivatives of mevalonate ...
During biotin deficiency, HMB can be synthesized from MC-CoA via enoyl-CoA hydratase and an unknown thioesterase enzyme, which ... a serine-threonine protein kinase that regulates protein biosynthesis and cell growth. The activation of mTOR by leucine is ... is then cleaved into acetyl-CoA and acetoacetate by HMG-CoA lyase or used in the production of cholesterol via the mevalonate ...
... nuclear located protein kinase C and cyclic AMP-dependent protein kinase". Frontiers in Bioscience. 13 (13): 1206-1226. doi: ... In animals and archaea, the mevalonate pathway produces these compounds from acetyl-CoA, while in plants and bacteria the non- ... "Biological roles of sulfoglycolipids and pathophysiology of their deficiency". Glycoconjugate Journal. 21 (1-2): 59-62. doi: ... Grochowski LL, Xu H, White RH (May 2006). "Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis of ...
Mevalonate then undergoes three series of reactions with one ATP dedicated to each to form mevalonate-5-PP. Mevalonate-5-PP ... It is believed that limitations induced by nitrogen deficiency within the medium can pause cell division, which causes a change ... This was accomplished via overexpressing heterologous xylulose kinase and endogenous xylose isomerase. A European patent has ... To form mevalonate (a precursor to sterols and carotenoids), two acetyl-CoAs combine to form acetoacetyl-CoA, then another ...
... deficiency (MCTD1) is an autosomal dominant and recessive disease on the SLC16A1/MCT1 gene on ... a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its ... and elevated serum creatine kinase. ENSG00000281917 GRCh38: Ensembl release 89: ENSG00000155380, ENSG00000281917 - Ensembl, May ... "MONOCARBOXYLATE TRANSPORTER 1 DEFICIENCY; MCT1D". omim.org. Retrieved 2023-08-21. "ERYTHROCYTE LACTATE TRANSPORTER DEFECT". ...
Beta-carotene, a substance typically associated with carrots that prevents vitamin A deficiency, is produced by rice that has ... Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (July 2003). "Engineering a mevalonate pathway in Escherichia coli for ... August 2012). "Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells". Nature. 488 (7411): ... Every year, between 250,000 and 500,000 children lose their vision due to vitamin A deficiency, which also significantly raises ...
"Mevalonate Kinase Deficiency". Mulders-Manders, CM; Simon, A (2015). "Hyper-IgD syndrome/mevalonate kinase deficiency: what is ... Mevalonate kinase deficiency is inherited in an autosomal recessive manner, meaning that a child must inherit a defective copy ... Mevalonate kinase deficiency causes an accumulation of mevalonic acid in the urine, resulting from insufficient activity of the ... Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol ...
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy ... Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have ... medlineplus.gov/genetics/condition/mevalonate-kinase-deficiency/ Mevalonate kinase deficiency. ... Mutations in the MVK gene cause mevalonate kinase deficiency. The MVK gene provides instructions for making the mevalonate ...
Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome, characterized by febrile episodes and generalized ... Genetic and phenotypic characteristics of 114 patients with mevalonate kinase deficiency. *J Jeyaratnam1, ... Genetic and phenotypic characteristics of 114 patients with mevalonate kinase deficiency. Pediatr Rheumatol 13 (Suppl 1), P25 ( ...
Perinatal onset mevalonate kinase deficiency.﻽. Steiner LA, Ehrenkranz RA, Peterec S, Steiner RD, Reyes-Múgica M, Gallagher P ...
Haas, D. & Hoffmann, G. F. Mevalonate kinase deficiency and autoinflammatory disorders. https://www.nejm.org/doi/10.1056/ ... deficiency and/or absence may differ amongst another ethnicity/population. Besides, the cut-off limit of isoprene deficiency in ... Surprisingly, while significant deficiency or absence of non-sterol C5H8 is reported in cases with inherited diseases like ... Previously we observed IDI1 but not IDI2 gene expression in PBMC of healthy adults with absence, deficiency, and normal breath ...
Mevalonate kinase deficiency: Evidence for a phenotypic continuum. Neurology. 2004 Mar 23. 62 (6):994-7. [QxMD MEDLINE Link]. ... Mevalonate kinase is the first enzyme to follow 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the mevalonate ... 39] HIDS is caused by mutations in the MVK gene, on chromosome 12, which encodes mevalonate kinase. [39] The carrier frequency ... Mevalonate kinase (MK) catalyzes the phosphorylation of mevalonic acid. This pathway is used to synthesize cholesterol and ...
... also known as mevalonate kinase deficiency; and familial Mediterranean fever.. Canakinumab was previously approved for ...
For the treatment of hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) when all of the following ... Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD) - Ilaris is indicated for the treatment of HIDS and ... in patients with mevalonate kinase deficiency (MKD). A questionnaire was sent to French pediatric and adult rheumatologists to ... Mevalonate Kinase Deficiency (MKD) and Familial Mediterranean Fever (FMF) (Novartis, 2016). All three conditions plus CAPS are ...
Mevalonate kinase deficiency (aka Hyper IgD syndrome).. *Cryopyrin associated periodic fever syndrome (CAPS). ... In rheumatology we collaborate with specialists in genetics, immune deficiency, and hematology at Cleveland Clinic Childrens ...
... mevalonate kinase deficiency (MKD). Ilaris is indicated for the treatment of hyperimmunoglobulin D syndrome (HIDS)/mevalonate ...
3, 2022 A new study offers insights into understanding the inflammatory disorder mevalonate kinase deficiency, and reveals new ...
New insights into the link between protein prenylation and inflammation using models of mevalonate kinase deficiency (MKD) ...
Mevalonic aciduria (MA), the most severe form of mevalonate kinase deficiency (MKD), is still an orphan drug disease and the ...
Mevalonate Kinase Deficiency (MKD), or Familial Mediterranean Fever (FMF)] *A diagnosis of tumor necrosis factor receptor ... A diagnosis of hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD); OR ... Mevalonate Kinase Deficiency (MKD), Familial Mediterranean Fever (FMF), Systemic Juvenile Idiopathic Arthritis (SJIA), or Adult ... Enzyme assay demonstrating a deficiency of beta-glucuronidase (GUS) activity; OR *Genetic testing to confirm diagnosis of MPS ...
251170 Mevalonate kinase; MVK. Cross references. Phenotypically related immunodeficiencies. IDR factfile for Familial ... Defects in mavalonate kinase (MVK) are the cause of mevalonicaciduria. It is an accumulation of mevalonic acid which cause a ...
Mevalonate kinase deficiency. Weekly.PI3K, Akt) may also be of benefit grade selected patients. -C. Pacala, S. 22 Foundations ... 1999) Agonist-dependent phosphorylation of the G pro- tein-coupled receptor kinase 2 (GRK2) by Src tyrosine kinase. We use the ...
mevalonate kinase deficiency. *mevalonic aciduria, see mevalonate kinase deficiency. *mevalonicaciduria, see mevalonate kinase ... MCAD deficiency, see medium-chain acyl-CoA dehydrogenase deficiency. *MCADD, see medium-chain acyl-CoA dehydrogenase deficiency ... multiple carboxylase deficiency, late-onset, see biotinidase deficiency. *Multiple Carboxylase Deficiency, Neonatal Form, see ... MAD deficiency, see adenosine monophosphate deaminase deficiency. *MADA deficiency, see adenosine monophosphate deaminase ...
It is used to treat cryopyrin-associated periodic syndromes, familial mediterranean fever, juvenile arthritis, and mevalonate ... kinase deficiency in the USA. It has been approved in Europe to treat cryopyrin-associated periodic syndromes, gouty arthritis ... and mevalonate kinase deficiency in the USA. It has been approved in Europe to treat cryopyrin-associated periodic syndromes, ...
Integrative multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency. Carapito R, ...
... mevalonate kinase deficiency; MWS, Muckle-Wells syndrome; NOMID, neonatal-onset multisystem inflammatory disease; NSAID, non- ...
... mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the ... The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR ...
Hyperimmunoglobulin D Syndrome (HIDS) also known as Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients ... Hyperimmunoglobulin D Syndrome (HIDS) also known as Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients ...
van der Burgh R, ter Haar NM, Boes ML, Frenkel J. Mevalonate kinase deficiency, a metabolic autoinflammatory disease. Clinical ... Mevalonate kinase deficiency Evidence for a phenotypic continuum. Neurology. 2004;62(6):994-7. ... Zhang S. Natural history of mevalonate kinase deficiency: a literature review. Pediatric Rheumatology. 2016;14(1):30. ... Leukocyte adhesion deficiency type II: long-term follow-up and review of the literature. J Clin Immunol. 2010 Mar;30(2):308-13 ...
... also known as Mevalonate Kinase Deficiency is a very rare autoinflammatory condition that usually begins in childhood ... HIDS (or hyperimmunoglobulinemia D syndrome) is also known as Mevalonate Kinase Deficiency (MKD). It is a very rare ... causes a drop in the levels of mevalonate kinase in the body. This deficiency creates a chain reaction that leads to an ... "mevalonate kinase deficiency" should replace HIDS as the name of the condition.9,10 ...
Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There ... Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy ... are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more ... The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form ...
... mevalonate kinase deficiency/MKD, NLRP12 associated autoinflammatory disorder, pyogenic arthritis pyoderma gangrenosum and ... mevalonate kinase deficiency/MKD, NLRP12 associated autoinflammatory disorder, pyogenic arthritis pyoderma gangrenosum and ... of all cases of mevalonate kinase deficiency (Takada et. al. 2003; Cuisset et. al. 2001; Zhang et. al. 2015). ... 1999). In patients with biochemical evidence of impaired mevalonate kinase activity and suspected Hyper-IgD syndrome or ...
Mevalonate Kinase Deficiency (MKD) and Familial Mediterranean Fever (FMF). ...
Mevalonate Kinase Deficiency:complications,. Citation OBJECTIVES: To present clinical and laboratory findings in the case of a ... OBJECTIVE: Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of ...
Mevalonate Kinase Deficiency. The febrile period is accompanied by lymphadenopathy, arthralgia, abdominal pain, diarrhea, ...
  • There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA). (medlineplus.gov)
  • HIDS (or hyperimmunoglobulinemia D syndrome) is also known as Mevalonate Kinase Deficiency (MKD). (autoinflammatorydiseases.com)
  • However, it is known that those with HIDS/MKD have a mutation in the MVK (mevalonate kinase) gene, a protein involved in the production of cholesterol in the body. (autoinflammatorydiseases.com)
  • 1,7 This genetic change, which is thought to be the main underlying problem in HIDS, causes a drop in the levels of mevalonate kinase in the body. (autoinflammatorydiseases.com)
  • 12 In fact, it has been suggested that the term "mevalonate kinase deficiency" should replace HIDS as the name of the condition. (autoinflammatorydiseases.com)
  • Virtually all people with the syndrome have mutations in the gene for mevalonate kinase, which is part of the HMG-CoA reductase pathway, an important cellular metabolic pathway. (wikipedia.org)
  • Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome, characterized by febrile episodes and generalized inflammation. (biomedcentral.com)
  • Mevalonate kinase deficiency (aka Hyper IgD syndrome). (clevelandclinic.org)
  • Neuromascular abnormality presenting with ataxia(ataxia-telangiectasia) , flaccid paralysis after live poliovirus immunization (combined or antibody deficiencies) ,pernicious anaemia (CVID), cognitive impairment, nystagmus and cerebellar, spinal and peripheral neuropathies(Chediac-Higashi syndrome), seizures, ataxia and occulomotor and reflex abnormalities(Griscelli syndrome) are examples of neurologic features seen in different immunodeficiency syndromes. (ac.ir)
  • Mevalonate kinase (MVK) is an enzyme involved in biosynthesis of cholesterols and isoprenoids and is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+. (wikipedia.org)
  • MKD is due to a mutation in the gene that encodes mevalonate kinase which results in a reduced or deficient activity of this enzyme. (wikipedia.org)
  • The MVK gene provides instructions for making the mevalonate kinase enzyme. (medlineplus.gov)
  • into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. (medlineplus.gov)
  • Lovastatin, blocks the mevalonate pathway inhibiting the 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR), an enzyme of the mevalonate pathway upstream the mevalonate kinase enzyme, reproducing biochemical features similar to those found in MKD. (unife.it)
  • It is used to treat cryopyrin-associated periodic syndromes, familial mediterranean fever, juvenile arthritis, and mevalonate kinase deficiency in the USA. (pharmakb.com)
  • Patients with a deficiency of LPL or apo C-II show a dramatic accumulation of chylomicrons in the plasma (type I hyperlipoproteinemia, or familial LPL deficiency) even if fasted. (pharmacy180.com)
  • It is not known how mevalonate kinase mutations cause the febrile episodes, although it is presumed that other products of the cholesterol biosynthesis pathway, the prenylation chains (geranylgeraniol and farnesol) might play a role. (wikipedia.org)
  • Mutations in the MVK gene cause mevalonate kinase deficiency. (medlineplus.gov)
  • Mevalonate kinase deficiency is inherited in an autosomal recessive manner, meaning that a child must inherit a defective copy of the gene from both parents to be affected. (wikipedia.org)
  • The gene which codes for mevalonate kinase consists of 10 exons at locus 12q14. (wikipedia.org)
  • Mevalonate kinase also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification. (medlineplus.gov)
  • The result of weighted gene co-expression network analysis (WGCNA) showed that growth years significantly affected the gene expression of Mitogen-activated protein kinases (MAPK) signaling pathway and terpenoid backbone biosynthesis pathway in cultivated ginseng, but had no effects in wild ginseng. (biomedcentral.com)
  • Because of this deficiency, mevalonic acid can build up in the body, with high levels found in the urine. (wikipedia.org)
  • Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. (medlineplus.gov)
  • Mevalonic aciduria (MA), the most severe form of mevalonate kinase deficiency (MKD), is still an orphan drug disease and the pathogenetic mechanisms underlying neuronal dysfunction is still poorly understood. (unife.it)
  • The rate-limiting and regulated step in cholesterol synthesis is catalyzed by the smooth endoplasmic reticulum-membrane protein, hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, which produces mevalonate from HMG CoA. (pharmacy180.com)
  • The presence of geranylgeraniol modulates both the caspase-9 and caspase-3 activity in a dose-dependent way, confirming that this isoprenoid enters the mevalonate pathway, is metabolized and finally is able to by-pass the statin biochemical block reconstituting the mevalonate pathway. (unife.it)
  • Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. (wikipedia.org)
  • Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. (medlineplus.gov)
  • In a human monocytic MKD model it was found that the deficiency of GGPP leads to overproduction of IL-1β and defective prenylation of RhoA. (wikipedia.org)
  • This deficiency creates a chain reaction that leads to an overproduction of cytokines, most prominently interleukin-1 beta (IL-1β). (autoinflammatorydiseases.com)
  • Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. (medlineplus.gov)
  • Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids. (medlineplus.gov)
  • It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. (medlineplus.gov)
  • The abnormal urinary loss of TRYPTOPHAN, a precursor of NIACIN, leads to a NICOTINAMIDE deficiency, PELLAGRA-like light-sensitive rash, CEREBELLAR ATAXIA, emotional instability, and aminoaciduria. (uchicago.edu)
  • MKD is caused by mutations in the gene encoding mevalonate kinase, with the degree of residual enzyme activity largely determining disease severity. (nih.gov)
  • Mevalonate Kinase Deficiency (MKD) is one of the autoinflammatory fever syndromes, caused by mutations in the MKD gene. (biomedcentral.com)
  • Autosomal recessive disorder caused by mutations in the mevalonate kinase gene. (nih.gov)
  • Mevalonate kinase deficiency (MKD) is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. (wikipedia.org)
  • Mevalonate kinase deficiency is inherited in an autosomal recessive manner, meaning that a child must inherit a defective copy of the gene from both parents to be affected. (wikipedia.org)
  • Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. (nature.com)
  • Ca2+/calmodulin-dependent kinase II (CaMKII) is a serine/threonine protein kinase that modulates various cardiac diseases. (stanford.edu)
  • is a kinase enzyme , in particular a protein kinase , that phosphorylates the OH group of the amino-acid residues serine or threonine , which have similar side chains. (cloudfront.net)
  • In enzymology , the term serine/threonine protein kinase describes a class of enzymes in the family of transferases , that transfer phosphates to the oxygen atom of a serine or threonine side chain in proteins . (cloudfront.net)
  • was in fact, the first Ser/Thr protein kinase to be discovered (in 1959 by Krebs et al. ). (cloudfront.net)
  • The gene codes for a protein kinase. (cloudfront.net)
  • Areas covered: On one hand, shortage of isoprenoid compounds downstream of mevalonate led to a defective geranylgeranylation of RhoA/Rac proteins and increased caspase-1-dependent inflammation. (units.it)
  • The exact mechanism that causes inflammatory reactions such as fevers, skin rashes, elevated immune system proteins, and many other features of mevalonate kinase deficiency is unclear. (nih.gov)
  • Most of the MVK gene mutations that cause mevalonate kinase deficiency lead to changes in single protein building blocks (amino acids) in the mevalonate kinase enzyme. (nih.gov)
  • Most MVK gene mutations lead to the production of a mevalonate kinase enzyme that is unstable and folded into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. (nih.gov)
  • Because of this deficiency, mevalonic acid can build up in the body, with high levels found in the urine. (wikipedia.org)
  • Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. (medlineplus.gov)
  • This enzyme converts a substance called mevalonic acid into mevalonate-5-phosphate. (nih.gov)
  • Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. (bioblast.at)
  • into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. (medlineplus.gov)
  • Mevalonate kinase (MVK) is an enzyme involved in biosynthesis of cholesterols and isoprenoids and is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+. (wikipedia.org)
  • Mevalonate kinase is essential for the biosynthesis of nonsterol isoprenoids, which mediate protein prenylation. (nih.gov)
  • It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. (medlineplus.gov)
  • Although the precise pathogenesis of MKD remains unclear, increasing evidence suggests that deficiency in protein prenylation leads to innate immune activation and systemic hyperinflammation. (nih.gov)
  • Types include those acting directly as membrane-bound receptors ( Receptor protein serine/threonine kinase ) and intracellular kinases participating in Signal transduction . (cloudfront.net)
  • Human homologs of the AKT8 oncogenic protein were identified in 1987.By 1995 it had been found that Akt kinases function as mitogen-activated kinases downstream from cell surface receptors that activate phosphoinositide 3-kinase . (cloudfront.net)
  • Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase (usually through hydrophobic forces and ionic bonds ), a kinase is usually not specific to a single substrate, but instead can phosphorylate a whole 'substrate family' which share common recognition sequences. (cloudfront.net)
  • To rule out the possibility that the effects we observed on imatinib treatment resulted from inhibition of protein kinases other than BCR ABL, we monitored binding of Runx1 and Runx3 to the 24p3R promoter in 32D cells expressing the imatinib resistant BCR ABL mutant. (hdac-inhibitors.com)
  • Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. (medlineplus.gov)
  • Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids. (medlineplus.gov)
  • Serine/threonine kinases play a role in the regulation of cell proliferation, programmed cell death ( apoptosis ), cell differentiation, and embryonic development. (cloudfront.net)
  • Mechanistically, in addition to IKKβ (inhibitor of NF-κB [nuclear factor-κB] kinase subunit β), CaMKII-δ9, but not δ2, directly interacted with IκBα (NF-κB inhibitor α) with its feature exon 13-16-17 combination and increased IκBα phosphorylation and consequently elicited more pronounced activation of NF-κB signaling and inflammatory response. (stanford.edu)
  • In a human monocytic MKD model it was found that the deficiency of GGPP leads to overproduction of IL-1β and defective prenylation of RhoA. (wikipedia.org)
  • 7. Activation of type I phosphatidylinositol 4-phosphate 5-kinase isoforms by the Rho GTPases, RhoA, Rac1, and Cdc42. (nih.gov)
  • 8. Unprenylated RhoA contributes to IL-1β hypersecretion in mevalonate kinase deficiency model through stimulation of Rac1 activity. (nih.gov)
  • Introduction: Mevalonate Kinase Deficiency (MKD) is a rare inborn disease caused by the mutation of mevalonate kinase gene. (units.it)
  • Consequences of identifying XIAP deficiency in an adult patient with inflammatory bowel disease. (ecco-ibd.eu)
  • Remission of inflammatory bowel disease in glucose-6-phosphatase 3 deficiency by allogeneic haematopoietic stem cell transplantation. (ecco-ibd.eu)
  • CaMKII (Ca2+/calmodulin-dependent kinase II) plays a central role in cardiac ischemia/reperfusion (I/R) injury-an important therapeutic target for ischemic heart disease. (stanford.edu)
  • While the catalytic domain of these kinases is highly conserved , the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. (cloudfront.net)
  • PHEFREE studies the health, neurologic, cognitive, neuropsychiatric, patient-reported, and quality-of-life outcomes in individuals with inherited disorders involving elevated blood phenylalanine including phenylalanine hydroxylase deficiency (also known as phenylketonuria or PKU), defects in biopterin synthesis or recycling, or deficiency of the chaperone protein DNAJC12. (nih.gov)
  • Defects in mavalonate kinase (MVK) are the cause of mevalonicaciduria. (lu.se)
  • When the pseudosubstrate is removed, the kinase can perform its normal function. (cloudfront.net)
  • At least 350 of the 500+ human protein kinases are serine/threonine kinases (STK). (cloudfront.net)