MCID: MVL001
MIFTS: 53

Mevalonic Aciduria malady

Categories: Genetic diseases, Rare diseases, Eye diseases, Bone diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Mevalonic Aciduria

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Sources:
50OMIM, 11Disease Ontology, 46NIH Rare Diseases, 23GeneTests, 24Genetics Home Reference, 13DISEASES, 52Orphanet, 68UniProtKB/Swiss-Prot, 25GTR, 12diseasecard, 37MeSH, 66UMLS, 43NCIt, 29ICD10 via Orphanet, 38MESH via Orphanet, 67UMLS via Orphanet, 35MedGen, 60SNOMED-CT, 62The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Mevalonic Aciduria:

Name: Mevalonic Aciduria 50 11 46 24 13 52 68 25 12 66
Mevalonate Kinase Deficiency 11 46 23 24 37
Mevalonicaciduria 46 23 24
Hyperimmunoglobulin D with Periodic Fever 24 25
Hyperimmunoglobulinemia D 24 66
Complete Mevalonate Kinase Deficiency 52
 
Deficiency of Mevalonate Kinase 66
Periodic Fever, Dutch Type 24
Hyper Igd Syndrome 24
Mevalonate Kinase 12
Meva 68
Mva 52

Characteristics:

Orphanet epidemiological data:

52
mevalonic aciduria:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal

HPO:

62
mevalonic aciduria:
Inheritance: autosomal recessive inheritance


Classifications:



External Ids:

OMIM50 610377
Disease Ontology11 DOID:0050452
MeSH37 D054078
NCIt43 C84890
Orphanet52 ORPHA29
ICD10 via Orphanet29 E88.8
MESH via Orphanet38 D054078
UMLS via Orphanet67 C0342731, C1959626
MedGen35 C1959626

Summaries for Mevalonic Aciduria

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NIH Rare Diseases:46 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).  last updated: 2/6/2012

MalaCards based summary: Mevalonic Aciduria, also known as mevalonate kinase deficiency, is related to malaria and hyper-igd syndrome, and has symptoms including microcephaly, dolichocephaly and triangular face. An important gene associated with Mevalonic Aciduria is MVK (Mevalonate Kinase), and among its related pathways are cholesterol biosynthesis I and Regulation of cholesterol biosynthesis by SREBP (SREBF). Affiliated tissues include skin, liver and spleen, and related mouse phenotypes are integument and homeostasis/metabolism.

UniProtKB/Swiss-Prot:68 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.

Genetics Home Reference:24 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.

OMIM:50 Mevalonic aciduria, the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of... (610377) more...

Wikipedia:69 Mevalonate kinase deficiency, also called mevalonic aciduria and hyper immunoglobin D syndrome is an... more...

Related Diseases for Mevalonic Aciduria

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Graphical network of the top 20 diseases related to Mevalonic Aciduria:



Diseases related to mevalonic aciduria

Symptoms for Mevalonic Aciduria

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Symptoms by clinical synopsis from OMIM:

610377

Clinical features from OMIM:

610377

Symptoms:

 52 (show all 17)
  • large fontanelles
  • microcephaly
  • dolichocephaly
  • triangular face
  • low-set, posteriorly rotated ears
  • downslanted palpebral fissures
  • cataract
  • blue sclerae
  • intellectual disability
  • seizures
  • ataxia
  • muscular hypotonia
  • global developmental delay
  • splenomegaly
  • cerebral cortical atrophy
  • delayed skeletal maturation
  • short stature

HPO human phenotypes related to Mevalonic Aciduria:

(show all 49)
id Description Frequency HPO Source Accession
1 microcephaly hallmark (90%) HP:0000252
2 dolichocephaly hallmark (90%) HP:0000268
3 triangular face hallmark (90%) HP:0000325
4 downslanted palpebral fissures hallmark (90%) HP:0000494
5 seizures hallmark (90%) HP:0001250
6 muscular hypotonia hallmark (90%) HP:0001252
7 splenomegaly hallmark (90%) HP:0001744
8 cerebral cortical atrophy hallmark (90%) HP:0002120
9 delayed skeletal maturation hallmark (90%) HP:0002750
10 short stature hallmark (90%) HP:0004322
11 cognitive impairment hallmark (90%) HP:0100543
12 low-set, posteriorly rotated ears typical (50%) HP:0000368
13 cataract typical (50%) HP:0000518
14 blue sclerae typical (50%) HP:0000592
15 incoordination typical (50%) HP:0002311
16 kyphoscoliosis rare (5%) HP:0002751
17 large fontanelles HP:0000239
18 microcephaly HP:0000252
19 dolichocephaly HP:0000268
20 triangular face HP:0000325
21 posteriorly rotated ears HP:0000358
22 low-set ears HP:0000369
23 downslanted palpebral fissures HP:0000494
24 cataract HP:0000518
25 blue sclerae HP:0000592
26 nystagmus HP:0000639
27 edema HP:0000969
28 skin rash HP:0000988
29 muscular hypotonia HP:0001252
30 global developmental delay HP:0001263
31 cerebellar atrophy HP:0001272
32 failure to thrive HP:0001508
33 thrombocytopenia HP:0001873
34 leukocytosis HP:0001974
35 vomiting HP:0002013
36 diarrhea HP:0002014
37 cerebral atrophy HP:0002059
38 progressive cerebellar ataxia HP:0002073
39 agenesis of cerebellar vermis HP:0002335
40 lymphadenopathy HP:0002716
41 arthralgia HP:0002829
42 elevated hepatic transaminases HP:0002910
43 elevated serum creatine phosphokinase HP:0003236
44 short stature HP:0004322
45 normocytic hypoplastic anemia HP:0004819
46 fluctuating splenomegaly HP:0006268
47 fluctuating hepatomegaly HP:0006564
48 aciduria HP:0012072
49 morbilliform rash HP:0012282

UMLS symptoms related to Mevalonic Aciduria:


abdominal pain, arthralgia, diarrhea, exanthema, headache, vomiting, macular rash, erythema scarlatiniforme, mucocutaneous rash, nodular rash

Drugs & Therapeutics for Mevalonic Aciduria

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Canakinumab in Patients With Active Hyper-IgD SyndromeCompletedNCT01303380Phase 2
2MEVALONATE KINASE GENE MUTATIONS AND THEIR CLINICAL CORRELATIONS IN BEHÇET'S DISEASECompletedNCT01780363
3Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase DeficiencyRecruitingNCT00260299
4B7 Coreceptor Molecules in Hyper IgD Syndrome Form of Mevalonate Kinase DeficiencyRecruitingNCT01568736

Search NIH Clinical Center for Mevalonic Aciduria


Cochrane evidence based reviews: mevalonate kinase deficiency

Genetic Tests for Mevalonic Aciduria

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Genetic tests related to Mevalonic Aciduria:

id Genetic test Affiliating Genes
1 Hyperimmunoglobulin D with Periodic Fever25
2 Mevalonic Aciduria25
3 Mevalonicaciduria23 MVK

Anatomical Context for Mevalonic Aciduria

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MalaCards organs/tissues related to Mevalonic Aciduria:

34
Skin, Liver, Spleen, Bone, Eye, Bone marrow

Animal Models for Mevalonic Aciduria or affiliated genes

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MGI Mouse Phenotypes related to Mevalonic Aciduria:

39
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00107717.8CASP1, DHCR24, IL1RN, NLRP3, SC5D
2MP:00053766.7CASP1, DHCR24, GALK1, HMGCR, IL1RN, NLRP3

Publications for Mevalonic Aciduria

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Articles related to Mevalonic Aciduria:

(show all 38)
idTitleAuthorsYear
1
Liver transplantation followed by allogeneic hematopoietic stem cell transplantation for atypical mevalonic aciduria. (22405037)
2012
2
Severe phenotypic spectrum of mevalonate kinase deficiency with minimal mevalonic aciduria. (23146290)
2012
3
Retinitis pigmentosa and punctate cataracts in mevalonic aciduria. (25390116)
2010
4
Conjugated hyperbilirubinaemia as the first manifestation of mevalonic aciduria in a term newborn. (20027140)
2009
5
Coenzyme Q(10) is decreased in fibroblasts of patients with methylmalonic aciduria but not in mevalonic aciduria. (19504350)
2009
6
The lack of non-steroid isoprenoids causes oxidative stress in patients with mevalonic aciduria. (18037572)
2008
7
Abnormal prenatal ultrasound findings in mevalonic aciduria. (18264963)
2008
8
Allogeneic bone marrow transplantation in mevalonic aciduria. (17596604)
2007
9
Mevalonic aciduria cured by bone marrow transplantation. (17898110)
2007
10
Mevalonic aciduria: report of two cases. (17578678)
2007
11
Coenzyme Q10 in phenylketonuria and mevalonic aciduria. (17442628)
2007
12
Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome. (16722536)
2006
13
First-trimester enzymatic and molecular prenatal diagnosis of mevalonic aciduria. (16435209)
2005
14
Novel genotype of mevalonic aciduria with fatalities in premature siblings. (14711867)
2004
15
An intestinal obstruction in an eight-month-old child suffering from mevalonic aciduria. (12162608)
2002
16
Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. (11313768)
2001
17
Mevalonic aciduria and hyper-IgD syndrome: two sides of the same coin? (11486910)
2001
18
Mevalonic aciduria in 12 unrelated patients with hyperimmunoglobulinaemia D and periodic fever syndrome. (10896295)
2000
19
Molecular basis of classical mevalonic aciduria and the hyperimmunoglobulinaemia D and periodic fever syndrome: high frequency of 3 mutations in the mevalonate kinase gene. (10896296)
2000
20
Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis. (10401001)
1999
21
Probing cataractogenesis associated with mevalonic aciduria. (9523093)
1998
22
Mevalonate kinase deficiency in a dizygotic twin with mild mevalonic aciduria. (9266363)
1997
23
Enhanced excretion of urinary leukotriene E4 in mevalonic aciduria is not caused by an impaired peroxisomal degradation of cysteinyl leukotrienes. (9323576)
1997
24
Clinical and biochemical phenotype in 11 patients with mevalonic aciduria. (8386351)
1993
25
Bile acid metabolism in three patients with mevalonic aciduria due to mevalonate kinase deficiency. (8261631)
1993
26
Mevalonic aciduria in 3 siblings: a new recognizable metabolic encephalopathy. (8352861)
1993
27
Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria. (1377680)
1992
28
Mevalonate kinase assay using DEAE-cellulose column chromatography for first-trimester prenatal diagnosis and complementation analysis in mevalonic aciduria. (1331607)
1992
29
Facts and artefacts in mevalonic aciduria: development of a stable isotope dilution GCMS assay for mevalonic acid and its application to physiological fluids, tissue samples, prenatal diagnosis and carrier detection. (1653652)
1991
30
Mevalonic aciduria. (1653382)
1991
31
Mevalonate kinase in lysates of cultured human fibroblasts and lymphoblasts: kinetic properties, assay conditions, carrier detection and measurement of residual activity in a patient with mevalonic aciduria. (2543551)
1989
32
A patient with mevalonic aciduria presenting with hepatosplenomegaly, congenital anaemia, thrombocytopenia and leukocytosis. (3141709)
1988
33
Mevalonate kinase deficiency in a child with cerebellar ataxia, hypotonia and mevalonic aciduria. (2850914)
1988
34
Mevalonic aciduria: pathobiochemical effects of mevalonate kinase deficiency on cholesterol metabolism in intact fibroblasts. (2846965)
1988
35
Mevalonic aciduria. (3338715)
1988
36
Near normal levels of isoprenoid lipids in severe mevalonic aciduria. (3365255)
1988
37
Mevalonic aciduria--an inborn error of cholesterol and nonsterol isoprene biosynthesis. (3012338)
1986
38
Mevalonic aciduria: an inborn error of cholesterol biosynthesis? (4053401)
1985

Variations for Mevalonic Aciduria

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UniProtKB/Swiss-Prot genetic disease variations for Mevalonic Aciduria:

68
id Symbol AA change Variation ID SNP ID
1MVKp.His20ProVAR_004022rs104895295
2MVKp.Ile268ThrVAR_004024rs104895304
3MVKp.Asn301ThrVAR_004025rs28934896
4MVKp.Ala334ThrVAR_004026rs104895317
5MVKp.Val310MetVAR_009068rs104895319
6MVKp.Thr243IleVAR_010964rs104895314
7MVKp.Leu264PheVAR_010965rs104895315
8MVKp.Leu265ProVAR_010966rs104895316

Clinvar genetic disease variations for Mevalonic Aciduria:

5
id Gene Variation Type Significance SNP ID Assembly Location
1MVKNM_000431.3(MVK): c.902A> C (p.Asn301Thr)single nucleotide variantPathogenicrs121917789GRCh37Chr 12, 110032849: 110032849
2MVKNM_000431.3(MVK): c.1129G> A (p.Val377Ile)single nucleotide variantPathogenicrs28934897GRCh37Chr 12, 110034320: 110034320
3MVKNM_000431.3(MVK): c.1000G> A (p.Ala334Thr)single nucleotide variantPathogenicrs104895317GRCh37Chr 12, 110032947: 110032947
4MVKNM_000431.3(MVK): c.59A> C (p.His20Pro)single nucleotide variantPathogenicrs104895295GRCh37Chr 12, 110012686: 110012686
5MVKNM_000431.3(MVK): c.803T> C (p.Ile268Thr)single nucleotide variantPathogenicrs104895304GRCh37Chr 12, 110029080: 110029080
6MVKNM_000431.3(MVK): c.928G> A (p.Val310Met)single nucleotide variantPathogenicrs104895319GRCh37Chr 12, 110032875: 110032875
7MVKNM_000431.3(MVK): c.16_34del (p.Leu6Glyfs)deletionPathogenicrs104895334GRCh37Chr 12, 110012643: 110012661
8MVKNM_000431.3(MVK): c.604G> A (p.Gly202Arg)single nucleotide variantPathogenicrs104895301GRCh37Chr 12, 110023903: 110023903
9MVKNM_000431.3(MVK): c.417dupC (p.Gly140Argfs)duplicationPathogenicrs104895373GRCh37Chr 12, 110019245: 110019245
10MVKNM_000431.3(MVK): c.72dupT (p.Gly25Trpfs)duplicationPathogenicrs104895322GRCh37Chr 12, 110012699: 110012699

Expression for genes affiliated with Mevalonic Aciduria

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Search GEO for disease gene expression data for Mevalonic Aciduria.

GO Terms for genes affiliated with Mevalonic Aciduria

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Cellular components related to Mevalonic Aciduria according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1NLRP3 inflammasome complexGO:00725599.1CASP1, NLRP3

Biological processes related to Mevalonic Aciduria according to GeneCards Suite gene sharing:

(show all 9)
idNameGO IDScoreTop Affiliating Genes
1isoprenoid biosynthetic processGO:000829910.1HMGCR, MVK
2cholesterol biosynthetic process via desmosterolGO:00334899.6DHCR24, SC5D
3negative regulation of inflammatory responseGO:00507289.6MVK, NLRP3
4cholesterol biosynthetic process via lathosterolGO:00334909.6DHCR24, SC5D
5interleukin-1 beta productionGO:00326119.6CASP1, NLRP3
6positive regulation of interleukin-1 beta secretionGO:00507189.5CASP1, NLRP3
7cholesterol biosynthetic processGO:00066959.3DHCR24, HMGCR, MVK
8regulation of inflammatory responseGO:00507279.1CASP1, NLRP3
9activation of cysteine-type endopeptidase activity involved in apoptotic processGO:00069198.8CASP1, NLRP3

Sources for Mevalonic Aciduria

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet