Mevalonic Aciduria (MEVA)

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Disease Ontology 12 DOID:0050452 OMIM 56 610377 KEGG 36 H00206 MeSH 43 D054078 NCIt 49 C84890 SNOMED-CT 67 124327008 234538002 718558008 ICD10 32 M04.1

MESH via Orphanet 44 D054078 ICD10 via Orphanet 33 E88.8 UMLS via Orphanet 72 C0342731 C1959626 Orphanet 58 ORPHA29 ORPHA309025 MedGen 41 C1959626 SNOMED-CT via HPO 68 111583006 123983008 128306009 128613002 16294009 166603001 166643006 193570009 204164000 20741006 224958001 228156007 230233000 237836003 246545002 246800008 247053007 247470007 247578003 249497008 253175003 253251006 258211005 267038008 267060006 271611007 276709006 278849000 300359004 302215000 30746006 313307000 36440009 398151007 398152000 405773007 415116008 418143002 422400008 423666004 432788009 50495000 52522001 563001 57676002 62315008 716997004 72239002 75183008 79654002 84757009 85102008 91138005 91175000 95515009 95646004 more UMLS 71 C0342731 C0398691 C1959626

Genetics Home Reference : ²⁵ Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often. Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. 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). During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why some people with HIDS have high levels of IgD and IgA and some do not. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy. People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.

MalaCards based summary : Mevalonic Aciduria, also known as mevalonate kinase deficiency, is related to hyper-igd syndrome and autoinflammatory syndrome, and has symptoms including vomiting, edema and arthralgia. An important gene associated with Mevalonic Aciduria is MVK (Mevalonate Kinase), and among its related pathways/superpathways are Terpenoid backbone biosynthesis and Innate Immune System. The drugs Colchicine and Immunoglobulins have been mentioned in the context of this disorder. Affiliated tissues include skin, liver and spleen, and related phenotypes are intellectual disability and global developmental delay

Disease Ontology : ¹² A peroxisomal disease that is characterized by cortical atrophy, microcephaly, dysmorphic facies, muscular hypotonia and intellectual disability and has material basis in mutation in the MVK gene that results in deficiency of mevalonate kinase and impaired cholesterol. biosynthesis.

NIH Rare Diseases : ⁵² Mevalonic aciduria is the severe form of mevalonate kinase deficiency, a condition characterized by recurrent episodes of fever that typically begin during infancy. During these fever episodes, people with mevalonic aciduria may have an enlarged liver and spleen (hepatosplenomegaly ), lymphadenopathy , abdominal pain, diarrhea, joint pain (arthralgia ), and skin rashes. Additional ongoing issues include developmental delay , progressive ataxia , progressive problems with vision, an unusually small, elongated head, and failure to thrive . Mevalonic aciduria is caused by deficiency of mevalonate kinase, the first committed enzyme of cholesterol biosynthesis. This deficiency occurs as a result of inherited mutations in the MVK gene . This condition is inherited in an autosomal recessive pattern. Treatment is challenging and remains mainly supportive. The less severe type of mevalonate kinase deficiency is called hyperimmunoglobulinemia D syndrome (HIDS).

OMIM : ⁵⁶ Mevalonic aciduria, the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of a deficiency of mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). Mevalonic acid accumulates because of failure of conversion to 5-phosphomevalonic acid, which is catalyzed by mevalonate kinase. Mevalonic acid is synthesized from 3-hydroxy-3-methylglutaryl-CoA, a reaction catalyzed by HMG-CoA reductase (142910). Mevalonic aciduria is characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and to periodic fever syndrome (HIDS; 260920), which is also caused by mutation in the MVK gene (summary by Prietsch et al., 2003). (610377)

KEGG : ³⁶ Mevalonate kinase deficiency is an autosomal recessive disorder, which is identified as the cause of two inherited human autoinflammatory disorders: mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS). Mevalonate kinase is located at the beginning of the cholesterol biosynthesis pathway compromising the biosynthesis of nonsterol isoprenes in addition to cholesterol. Patients of MVA show the symptoms, including dysmorphic features, cataracts, neurologic symptoms. The majority of patients with HIDS experience only recurrent febrile crises, without any neurologic abnormalities or dysmorphic features. Mevalonic kinase activity in HIDS patients is generally in the range of 5-15% of normal as compared to 0-4% in MVA.

UniProtKB/Swiss-Prot : ⁷³ Mevalonic aciduria: Accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia.

Wikipedia : ⁷⁴ Mevalonate kinase deficiency (MKD), is an autosomal recessive metabolic disorder that disrupts the... more...

Clinical features from OMIM:

610377

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.73	CASP1 NOD2 TNFRSF1B
2	Increased viability with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.73	CARD14 CASP1 IL18 IL1B NLRC4 NLRP3
3	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-1	9.44	IL18 IL1B NLRP3 TNF TNFRSF1A
4	Synthetic lethal with MLN4924 (a NAE inhibitor)	GR00250-A-2	9.44	CASP1 IL18 IL1B NLRP3 NOD2 TNF

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