MEVA
MCID: MVL001
MIFTS: 64

Mevalonic Aciduria (MEVA)

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

Aliases & Classifications for Mevalonic Aciduria

MalaCards integrated aliases for Mevalonic Aciduria:

Name: Mevalonic Aciduria 56 12 52 25 58 73 29 13 6 15 71
Mevalonate Kinase Deficiency 12 74 25 58 36 43
Hyperimmunoglobulin D with Periodic Fever 25 29 6
Mevalonicaciduria 74 52 25
Complete Mevalonate Kinase Deficiency 52 58
Hyperimmunoglobulinemia D 25 71
Meva 56 73
Mva 52 58
Deficiency of Mevalonate Kinase 71
Periodic Fever, Dutch Type 25
Aciduria, Mevalonic 39
Hyper Igd Syndrome 25

Characteristics:

Orphanet epidemiological data:

58
mevalonic aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
recurrent febrile crises with lymphadenopathy, hepatosplenomegaly, vomiting, and diarrhea
onset of crises in early childhood
febrile crises decrease with age, with ataxia becoming the predominant symptom (in some patients)
rash, edema, and arthralgia may occur during crisis
allelic to hyperimmunoglobulinemia d syndrome (hids, )


HPO:

31
mevalonic aciduria:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare systemic and rhumatological diseases
Rare skin diseases
Inborn errors of metabolism


Summaries for Mevalonic Aciduria

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, arthralgia and abdominal pain. 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 Antibodies, Monoclonal have been mentioned in the context of this disorder. Affiliated tissues include skin, kidney and liver, and related phenotypes are intellectual disability and seizures

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...

Related Diseases for Mevalonic Aciduria

Diseases related to Mevalonic Aciduria via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 282)
# Related Disease Score Top Affiliating Genes
1 hyper-igd syndrome 33.1 TNFRSF1A MVK IL1RN
2 autoinflammatory syndrome 30.9 NLRP3 NLRP12 NLRC4
3 relapsing fever 30.6 TNFRSF1A MVK MEFV
4 cryopyrin-associated periodic syndrome 30.5 NLRP3 IL1RN
5 systemic onset juvenile idiopathic arthritis 30.5 IL1RN IL1B
6 hereditary periodic fever syndrome 30.4 TNFRSF1A NLRP3 MEFV
7 amyloidosis 30.4 TNFRSF1A NLRP3 MEFV IL1RN
8 macrophage activation syndrome 30.2 TNFRSF1B TNFRSF1A NLRC4
9 aseptic meningitis 30.1 NLRP3 IL1RN IL1B
10 uveitis 30.1 TNFRSF1B TNFRSF1A NOD2
11 familial cold autoinflammatory syndrome 1 30.1 TNFRSF1A NLRP3 MEFV CASP1
12 wells syndrome 30.1 TNFRSF1A NLRP3 MEFV IL1B
13 exanthem 30.1 TNFRSF1B NLRP3 MEFV IL1RN
14 adult-onset still's disease 30.0 TNFRSF1A MEFV IL1RN IL1B
15 pericarditis 30.0 TNFRSF1A MEFV IL1RN IL1B
16 stomatitis 30.0 NLRP3 MEFV IL1RN IL1B
17 peritonitis 30.0 NLRP3 MEFV IL1B
18 bacterial infectious disease 29.8 NOD2 IL1RN IL1B CASP1
19 acquired immunodeficiency syndrome 29.8 TNFRSF1B TNFRSF1A IL1B CASP1
20 toxoplasmosis 29.8 NOD2 IL1B CASP1
21 juvenile rheumatoid arthritis 29.8 TNFRSF1B TNFRSF1A IL1RN IL1B
22 pharyngitis 29.6 TNFRSF1B NLRP3 MVK MEFV IL1RN IL1B
23 proteasome-associated autoinflammatory syndrome 1 29.6 TNFRSF1B NLRP3 MVK MEFV IL1RN IL1B
24 sarcoidosis 1 29.5 TNFRSF1B NOD2 IL1RN IL1B
25 multiple sclerosis 29.0 TNFRSF1B TNFRSF1A IL1RN IL1B HMGCR CASP1
26 malaria 29.0 TNFRSF1B TNFRSF1A NLRP3 NLRP12 IL1RN IL1B
27 familial mediterranean fever 28.9 TNFRSF1A PSTPIP1 NOD2 NLRP3 MVK MEFV
28 osteomyelitis 28.9 NOD2 NLRP3 LPIN2 IL1RN IL1B CASP1
29 inflammatory bowel disease 28.1 TNFRSF1B TNFRSF1A PSTPIP1 NOD2 NLRP3 MEFV
30 familial cold autoinflammatory syndrome 27.9 PSTPIP1 NOD2 NLRP3 NLRP12 NLRC4 MVK
31 periodic fever, familial, autosomal dominant 27.6 TNFRSF1B TNFRSF1A PSTPIP1 NOD2 NLRP3 NLRP12
32 muckle-wells syndrome 27.6 TNFRSF1A PSTPIP1 NOD2 NLRP3 NLRP12 NLRC4
33 cinca syndrome 27.5 TNFRSF1A PSTPIP1 NOD2 NLRP3 NLRP12 NLRC4
34 mosaic variegated aneuploidy syndrome 12.5
35 peho syndrome 11.4
36 mosaic variegated aneuploidy syndrome 1 11.4
37 mosaic variegated aneuploidy syndrome 3 11.2
38 vaccinia 11.1
39 smallpox 10.7
40 variola major 10.7
41 inflammatory myopathy with abundant macrophages 10.5 TNFRSF1A MEFV
42 intermittent hydrarthrosis 10.5 TNFRSF1A MEFV
43 human immunodeficiency virus type 1 10.4
44 idiopathic recurrent pericarditis 10.4 TNFRSF1A MEFV
45 ataxia and polyneuropathy, adult-onset 10.4
46 triiodothyronine receptor auxiliary protein 10.4
47 cataract 10.4
48 pouchitis 10.3 NOD2 IL1RN
49 aceruloplasminemia 10.3
50 autosomal recessive disease 10.3

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



Diseases related to Mevalonic Aciduria

Symptoms & Phenotypes for Mevalonic Aciduria

Human phenotypes related to Mevalonic Aciduria:

58 31 (show all 43)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0001250
3 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
4 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
5 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
6 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
7 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
8 downslanted palpebral fissures 58 31 hallmark (90%) Very frequent (99-80%) HP:0000494
9 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
10 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
11 dolichocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000268
12 large fontanelles 58 31 hallmark (90%) Very frequent (99-80%) HP:0000239
13 triangular face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000325
14 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
15 cataract 58 31 frequent (33%) Frequent (79-30%) HP:0000518
16 low-set, posteriorly rotated ears 58 31 frequent (33%) Frequent (79-30%) HP:0000368
17 blue sclerae 58 31 frequent (33%) Frequent (79-30%) HP:0000592
18 kyphoscoliosis 31 occasional (7.5%) HP:0002751
19 low-set ears 31 HP:0000369
20 failure to thrive 31 HP:0001508
21 nystagmus 31 HP:0000639
22 vomiting 31 HP:0002013
23 arthralgia 31 HP:0002829
24 generalized hypotonia 31 HP:0001290
25 edema 31 HP:0000969
26 elevated hepatic transaminase 31 HP:0002910
27 thrombocytopenia 31 HP:0001873
28 posteriorly rotated ears 31 HP:0000358
29 agenesis of cerebellar vermis 31 HP:0002335
30 leukocytosis 31 HP:0001974
31 diarrhea 31 HP:0002014
32 progressive cerebellar ataxia 31 HP:0002073
33 cerebellar atrophy 31 HP:0001272
34 lymphadenopathy 31 HP:0002716
35 cerebral atrophy 31 HP:0002059
36 psychomotor retardation 31 HP:0025356
37 aciduria 31 HP:0012072
38 morbilliform rash 31 HP:0012282
39 elevated serum creatine kinase 31 HP:0003236
40 normocytic hypoplastic anemia 31 HP:0004819
41 fluctuating splenomegaly 31 HP:0006268
42 fluctuating hepatomegaly 31 HP:0006564
43 increased circulating igd level 31 HP:0410246

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Head And Neck Eyes:
nystagmus
blue sclerae
downslanting palpebral fissures
central cataracts
nuclear cataract (in some patients) retinal dystrophy (in some patients)
more
Head And Neck Head:
microcephaly
dolichocephaly
wide, irregular fontanels

Skin Nails Hair Skin:
edema
morbilliform rash

Neurologic Central Nervous System:
agenesis of cerebellar vermis
cerebellar atrophy
cerebral atrophy
psychomotor retardation
developmental delay
more
Laboratory Abnormalities:
elevated serum creatine kinase
elevated transaminases
serum cholesterol low or normal
elevated leukotriene e(4)
decreased ubiquinone-10
more
Abdomen Liver:
fluctuating hepatomegaly

Skeletal Spine:
kyphoscoliosis (in some patients)

Growth Other:
failure to thrive

Growth Height:
short stature

Abdomen Gastrointestinal:
vomiting
diarrhea

Hematology:
thrombocytopenia
leukocytosis
normocytic hypoplastic anemia

Head And Neck Face:
triangular face

Abdomen Spleen:
fluctuating splenomegaly

Skeletal Limbs:
arthralgias

Immunology:
elevated igd

Clinical features from OMIM:

610377

UMLS symptoms related to Mevalonic Aciduria:


vomiting, arthralgia, abdominal pain, edema, headache, diarrhea

GenomeRNAi Phenotypes related to Mevalonic Aciduria according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.74 CASP1 IL1B NLRP3 NOD2 TNFRSF1A TNFRSF1B
2 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.74 CASP1 IL1B NLRP3 NOD2 TNFRSF1A TNFRSF1B
3 Decreased free cholesterol GR00340-A-2 9.13 HMGCR MMAB MVK

MGI Mouse Phenotypes related to Mevalonic Aciduria:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.21 CASP1 IL1B IL1RL2 IL1RN LPIN2 MEFV
2 cellular MP:0005384 10.2 CARD14 CASP1 IL1RN MEFV NLRC4 NLRP12
3 growth/size/body region MP:0005378 10.18 CARD14 HMGCR IL1B IL1RN LPIN2 MEFV
4 homeostasis/metabolism MP:0005376 10.17 CASP1 GALK1 HMGCR IL1B IL1RL2 IL1RN
5 immune system MP:0005387 10.13 CARD14 CASP1 IL1B IL1RL2 IL1RN LPIN2
6 digestive/alimentary MP:0005381 9.98 CASP1 NLRP12 NLRP3 NOD2 STING1 TNFRSF1A
7 integument MP:0010771 9.85 CARD14 CASP1 IL1B IL1RL2 IL1RN MEFV
8 mortality/aging MP:0010768 9.77 CARD14 CASP1 HMGCR IL1B IL1RN LPIN2
9 skeleton MP:0005390 9.28 IL1B IL1RN LPIN2 MEFV NLRC4 NLRP3

Drugs & Therapeutics for Mevalonic Aciduria

Drugs for Mevalonic Aciduria (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Colchicine Approved Phase 3 64-86-8 6167 2833
2 Antibodies, Monoclonal Phase 3
3 Immunologic Factors Phase 3
4 Immunoglobulins Phase 3
5 Antibodies Phase 3
6 Pharmaceutical Solutions Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 An Extension Study of CACZ885N2301 (NCT02059291), Multi-center, Open Label Study of Canakinumab in Japanese Patients With Periodic Fever Syndromes (Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyper Immunoglobulin D Syndrome ((Also Known as Mevalonate Kinase Deficiency) (HIDS/MKD), or Colchicine Resistant/Intolerant Familial Mediterranean Fever (crFMF)) Completed NCT02911857 Phase 3
2 A Randomized, Double-blind, Placebo Controlled Study of Canakinumab in Patients With Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), With Subsequent Randomized Withdrawal/Dosing Frequency Reduction and Open-label Long-term Treatment Epochs Completed NCT02059291 Phase 3 Canakinumab;Placebo
3 A French Open-label Extension Study of Canakinumab in Patients Who Participated in International Phase III Studies CACZ885G2301E1 or CACZ885G2306 in Systemic Juvenile Idiopathic Arthritis and CACZ885N2301 in Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF) Completed NCT02334748 Phase 3 canakinumab
4 An Open-label, Multicenter, Efficacy and Safety Pilot Study of 6-month Canakinumab Treatment With up to 6-month Follow-up in Patients With Active Hyper-IgD Syndrome (HIDS) Completed NCT01303380 Phase 2 Canakinumab
5 MEVALONATE KINASE GENE MUTATIONS AND THEIR CLINICAL CORRELATIONS IN BEHÇET'S DISEASE Completed NCT01780363
6 Genetics and Pathophysiology of Autoinflammatory Disorders. Recruiting NCT00001373
7 Creation of a Tool to Assess Quality of Life in Patient With Auto-inflammatory Diseases Active, not recruiting NCT03569644
8 Dietary Cholesterol and Defects in Cholesterol Synthesis in Mevalonate Kinase Deficiency Terminated NCT00260299
9 B7 Coreceptor Molecules as Clinically-Relevant Surrogate Biomarkers in the Hyper IgD Syndrome (HIDS) Form of Mevalonate Kinase Deficiency (MKD) Withdrawn NCT01568736

Search NIH Clinical Center for Mevalonic Aciduria

Cochrane evidence based reviews: mevalonate kinase deficiency

Genetic Tests for Mevalonic Aciduria

Genetic tests related to Mevalonic Aciduria:

# Genetic test Affiliating Genes
1 Hyperimmunoglobulin D with Periodic Fever 29 MVK
2 Mevalonic Aciduria 29 MVK

Anatomical Context for Mevalonic Aciduria

MalaCards organs/tissues related to Mevalonic Aciduria:

40
Skin, Kidney, Liver, Spleen, Eye, Lymph Node, Bone

Publications for Mevalonic Aciduria

Articles related to Mevalonic Aciduria:

(show top 50) (show all 287)
# Title Authors PMID Year
1
Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency. 61 56 6
16835861 2006
2
Mevalonate kinase deficiency: enlarging the clinical and biochemical spectrum. 61 56 6
12563048 2003
3
Clinical and biochemical phenotype in 11 patients with mevalonic aciduria. 61 56 6
8386351 1993
4
Mutations in the mevalonate kinase (MVK) gene cause nonsyndromic retinitis pigmentosa. 61 6
24084495 2013
5
Retinitis pigmentosa in mevalonate kinase deficiency. 61 6
16435210 2005
6
Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. 61 6
11313769 2001
7
Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis. 61 6
10401001 1999
8
Hematological abnormalities and cholestatic liver disease in two patients with mevalonate kinase deficiency. 61 56
9714005 1998
9
Mevalonic aciduria in 3 siblings: a new recognizable metabolic encephalopathy. 61 56
8352861 1993
10
Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria. 61 6
1377680 1992
11
Mevalonate kinase deficiency in a child with cerebellar ataxia, hypotonia and mevalonic aciduria. 61 56
2850914 1988
12
Mevalonic aciduria--an inborn error of cholesterol and nonsterol isoprene biosynthesis. 61 56
3012338 1986
13
Mevalonic aciduria: an inborn error of cholesterol biosynthesis? 61 56
4053401 1985
14
Exome sequencing identifies MVK mutations in disseminated superficial actinic porokeratosis. 6
22983302 2012
15
MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever. 6
15536479 2005
16
Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. 6
10369262 1999
17
Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. 6
10369261 1999
18
Performance of the new 'Eurofever/PRINTO classification criteria' in FMF patients. 61
31471011 2020
19
Mevalonic aciduria: Does stem cell transplant fully cure disease? 61
31651069 2020
20
What's new in autoinflammation? 61
30552566 2019
21
Mevalonate kinase deficiency masked by cytomegalovirus infection and obscure liver disease. 61
31430439 2019
22
Hereditary systemic autoinflammatory diseases and Schnitzler's syndrome. 61
31769858 2019
23
Targeting cytokines to treat autoinflammatory diseases. 61
30394352 2019
24
Dosage Considerations for Canakinumab in Children With Periodic Fever Syndromes. 61
30447083 2019
25
PAPA and FMF in two siblings: possible amplification of clinical presentation? A case report. 61
31443670 2019
26
Classification criteria for autoinflammatory recurrent fevers. 61
31018962 2019
27
When neonatal inflammation does not mean infection: an early-onset mevalonate kinase deficiency with interstitial lung disease. 61
31096039 2019
28
Immunometabolic function of cholesterol in cardiovascular disease and beyond. 61
31095280 2019
29
A case report of mevalonate kinase deficiency in a 14-month-old female with fevers and lower extremity weakness. 61
31325964 2019
30
Monocyte Production of IFN-γ Is Interleukin-12 Dependent in a Model of Mevalonate Kinase Deficiency. 61
31013450 2019
31
Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study. 61
30783801 2019
32
An International Delphi Survey for the Definition of New Classification Criteria for Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TNF Receptor-associated Periodic Fever Syndromes, and Cryopyrin-associated Periodic Syndrome. 61
30385706 2019
33
Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism? 61
30632494 2019
34
Canakinumab for the treatment of hyperimmunoglobulin D syndrome. 61
30652926 2019
35
Autoinflammatory diseases: State of the art. 61
30686513 2019
36
Evidence for a role of geranylgeranylation in renal angiomyolipoma and renal epithelioid angiomyolipoma. 61
30675208 2019
37
Defective Protein Prenylation in a Spectrum of Patients With Mevalonate Kinase Deficiency. 61
31474985 2019
38
National survey of Japanese patients with mevalonate kinase deficiency reveals distinctive genetic and clinical characteristics. 61
29451047 2019
39
Osteoporosis in Systemic Autoinflammatory Diseases: A Case-Control Study. 61
31620089 2019
40
In silico validation of the Autoinflammatory Disease Damage Index. 61
30077992 2018
41
Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency. 61
30030262 2018
42
Prolonged treatment with mevalonolactone induces oxidative stress response with reactive oxygen species production, mitochondrial depolarization and inflammation in human glioblastoma U-87 MG cells. 61
29753116 2018
43
The patient journey to diagnosis and treatment of autoinflammatory diseases. 61
30189864 2018
44
Respiratory deficiency in yeast mevalonate kinase deficient may explain MKD-associate metabolic disorder in humans. 61
29374778 2018
45
Hyper-immunoglobulin D syndrome with novel mutations in an afebrile infant. 61
29600537 2018
46
[Mevalonate kinase deficiency]. 61
29886611 2018
47
A Comprehensive Overview of the Hereditary Periodic Fever Syndromes. 61
27068928 2018
48
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. 61
29768139 2018
49
[Periodic fever syndromes]. 61
29808817 2018
50
Neuronal Dysfunction Associated with Cholesterol Deregulation. 61
29783748 2018

Variations for Mevalonic Aciduria

ClinVar genetic disease variations for Mevalonic Aciduria:

6 (show top 50) (show all 146) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MVK NM_000431.4(MVK):c.604G>A (p.Gly202Arg)SNV Pathogenic 39726 rs104895301 12:110023903-110023903 12:109586098-109586098
2 MVK NM_000431.3(MVK):c.417dupC (p.Gly140Argfs)duplication Pathogenic 39727 rs104895373 12:110019239-110019240 12:109581434-109581435
3 MVK NM_000431.3(MVK):c.72dupT (p.Gly25Trpfs)duplication Pathogenic 88836 rs104895322 12:110012698-110012699 12:109574893-109574894
4 MVK NM_000431.3(MVK):c.421dupG (p.Ala141Glyfs)duplication Pathogenic 88837 rs104895323 12:110019245-110019246 12:109581440-109581441
5 MVK NM_000431.4(MVK):c.1000G>A (p.Ala334Thr)SNV Pathogenic 11930 rs104895317 12:110032947-110032947 12:109595142-109595142
6 MVK NM_000431.4(MVK):c.59A>C (p.His20Pro)SNV Pathogenic 11931 rs104895295 12:110012686-110012686 12:109574881-109574881
7 MVK NM_000431.4(MVK):c.803T>C (p.Ile268Thr)SNV Pathogenic 11932 rs104895304 12:110029080-110029080 12:109591275-109591275
8 MVK NM_000431.4(MVK):c.494C>T (p.Pro165Leu)SNV Pathogenic 11933 rs121917790 12:110019322-110019322 12:109581517-109581517
9 MVK NM_000431.4(MVK):c.928G>A (p.Val310Met)SNV Pathogenic 11934 rs104895319 12:110032875-110032875 12:109595070-109595070
10 MVK NM_000431.4(MVK):c.16_34del (p.Leu6fs)deletion Pathogenic 11935 rs104895334 12:110012643-110012661 12:109574838-109574856
11 MVK NM_000431.4(MVK):c.902A>C (p.Asn301Thr)SNV Pathogenic 11928 rs121917789 12:110032849-110032849 12:109595044-109595044
12 MVK NM_000431.4(MVK):c.1162C>T (p.Arg388Ter)SNV Pathogenic 97572 rs104895360 12:110034353-110034353 12:109596548-109596548
13 MVK NM_000431.4(MVK):c.442G>A (p.Ala148Thr)SNV Pathogenic 97592 rs104895298 12:110019270-110019270 12:109581465-109581465
14 MVK NM_000431.4(MVK):c.564G>A (p.Trp188Ter)SNV Pathogenic 97597 rs104895311 12:110023863-110023863 12:109586058-109586058
15 MVK NM_000431.4(MVK):c.709A>T (p.Thr237Ser)SNV Pathogenic 97612 rs104895366 12:110028607-110028607 12:109590802-109590802
16 MVK NM_000431.4(MVK):c.830G>A (p.Arg277His)SNV Pathogenic 97631 rs104895352 12:110029107-110029107 12:109591302-109591302
17 MVK NM_000431.4(MVK):c.58C>A (p.His20Asn)SNV Pathogenic 649235 12:110012685-110012685 12:109574880-109574880
18 MVK NM_000431.4(MVK):c.545T>A (p.Leu182Ter)SNV Pathogenic 573681 rs1566147222 12:110023844-110023844 12:109586039-109586039
19 MVK NM_000431.4(MVK):c.608T>C (p.Val203Ala)SNV Pathogenic/Likely pathogenic 97601 rs104895332 12:110023907-110023907 12:109586102-109586102
20 MVK NM_000431.4(MVK):c.346T>C (p.Tyr116His)SNV Pathogenic/Likely pathogenic 97581 rs104895382 12:110017726-110017726 12:109579921-109579921
21 MVK NM_000431.4(MVK):c.500C>T (p.Pro167Leu)SNV Likely pathogenic 39725 rs104895300 12:110019328-110019328 12:109581523-109581523
22 MVK NM_000431.4(MVK):c.687_688TC[1] (p.Leu230fs)short repeat Likely pathogenic 802890 12:110028584-110028585 12:109590779-109590780
23 MVK NM_000431.4(MVK):c.768+4A>GSNV Likely pathogenic 488556 rs1295630463 12:110028670-110028670 12:109590865-109590865
24 MVK NM_000431.4(MVK):c.780C>A (p.Ile260=)SNV Conflicting interpretations of pathogenicity 307099 rs34975996 12:110029057-110029057 12:109591252-109591252
25 MVK NM_000431.4(MVK):c.591C>T (p.His197=)SNV Conflicting interpretations of pathogenicity 97599 rs104895329 12:110023890-110023890 12:109586085-109586085
26 MVK NM_000431.4(MVK):c.381G>A (p.Pro127=)SNV Conflicting interpretations of pathogenicity 138313 rs140397628 12:110019209-110019209 12:109581404-109581404
27 MVK NM_000431.4(MVK):c.-15+11G>ASNV Conflicting interpretations of pathogenicity 307090 rs192335177 12:110011689-110011689 12:109573884-109573884
28 MVK NM_000431.4(MVK):c.1005C>T (p.Gly335=)SNV Conflicting interpretations of pathogenicity 97560 rs104895357 12:110032952-110032952 12:109595147-109595147
29 MVK NM_000431.4(MVK):c.1129G>A (p.Val377Ile)SNV Conflicting interpretations of pathogenicity 11929 rs28934897 12:110034320-110034320 12:109596515-109596515
30 MVK NM_000431.4(MVK):c.1139A>G (p.His380Arg)SNV Conflicting interpretations of pathogenicity 97569 rs104895324 12:110034330-110034330 12:109596525-109596525
31 MVK NM_000431.4(MVK):c.238G>A (p.Val80Ile)SNV Conflicting interpretations of pathogenicity 97578 rs76914224 12:110017618-110017618 12:109579813-109579813
32 MVK NM_000431.4(MVK):c.277_283del (p.Glu93fs)deletion Uncertain significance 97579 rs104895369 12:110017656-110017662 12:109579851-109579857
33 MVK NM_000431.4(MVK):c.1067C>T (p.Thr356Met)SNV Uncertain significance 97564 rs104895342 12:110034258-110034258 12:109596453-109596453
34 MVK NM_000431.4(MVK):c.371+13T>CSNV Uncertain significance 307095 rs201201471 12:110017764-110017764 12:109579959-109579959
35 MVK NM_000431.4(MVK):c.527+8T>CSNV Uncertain significance 307096 rs377547988 12:110019363-110019363 12:109581558-109581558
36 MVK NM_000431.4(MVK):c.527+13C>ASNV Uncertain significance 307097 rs199670546 12:110019368-110019368 12:109581563-109581563
37 MVK NM_000431.4(MVK):c.1163G>A (p.Arg388Gln)SNV Uncertain significance 307101 rs886048934 12:110034354-110034354 12:109596549-109596549
38 MVK NM_000431.4(MVK):c.*75T>GSNV Uncertain significance 307103 rs138924471 12:110034457-110034457 12:109596652-109596652
39 MVK NM_000431.4(MVK):c.*412C>TSNV Uncertain significance 307106 rs192656516 12:110034794-110034794 12:109596989-109596989
40 MVK NM_000431.4(MVK):c.-55G>CSNV Uncertain significance 307087 rs886048929 12:110011638-110011638 12:109573833-109573833
41 MVK NM_000431.4(MVK):c.-33G>ASNV Uncertain significance 307088 rs886048930 12:110011660-110011660 12:109573855-109573855
42 MVK NM_000431.4(MVK):c.-15G>ASNV Uncertain significance 307089 rs567278499 12:110011678-110011678 12:109573873-109573873
43 MVK NM_000431.4(MVK):c.302G>A (p.Cys101Tyr)SNV Uncertain significance 307092 rs886048931 12:110017682-110017682 12:109579877-109579877
44 MVK NM_000431.4(MVK):c.78+8G>ASNV Uncertain significance 307091 rs766391278 12:110012713-110012713 12:109574908-109574908
45 MVK NM_000431.4(MVK):c.*431C>TSNV Uncertain significance 307107 rs72648044 12:110034813-110034813 12:109597008-109597008
46 MVK NM_000431.4(MVK):c.*468C>TSNV Uncertain significance 307108 rs768794506 12:110034850-110034850 12:109597045-109597045
47 MVK NM_000431.4(MVK):c.317G>A (p.Arg106His)SNV Uncertain significance 307093 rs778337320 12:110017697-110017697 12:109579892-109579892
48 MVK NM_000431.4(MVK):c.331G>A (p.Ala111Thr)SNV Uncertain significance 307094 rs371257609 12:110017711-110017711 12:109579906-109579906
49 MVK NM_000431.4(MVK):c.598C>T (p.Pro200Ser)SNV Uncertain significance 307098 rs886048932 12:110023897-110023897 12:109586092-109586092
50 MVK NM_000431.4(MVK):c.*308G>ASNV Uncertain significance 307104 rs886048935 12:110034690-110034690 12:109596885-109596885

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

73
# Symbol AA change Variation ID SNP ID
1 MVK p.His20Pro VAR_004022 rs104895295
2 MVK p.Ile268Thr VAR_004024 rs104895304
3 MVK p.Asn301Thr VAR_004025 rs121917789
4 MVK p.Ala334Thr VAR_004026 rs104895317
5 MVK p.Val310Met VAR_009068 rs104895319
6 MVK p.Thr243Ile VAR_010964 rs104895314
7 MVK p.Leu264Phe VAR_010965 rs104895315
8 MVK p.Leu265Pro VAR_010966 rs104895316

Expression for Mevalonic Aciduria

Search GEO for disease gene expression data for Mevalonic Aciduria.

Pathways for Mevalonic Aciduria

Pathways related to Mevalonic Aciduria according to KEGG:

36
# Name Kegg Source Accession
1 Terpenoid backbone biosynthesis hsa00900

Pathways related to Mevalonic Aciduria according to GeneCards Suite gene sharing:

(show all 21)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.83 TNFRSF1B TNFRSF1A STING1 PSTPIP1 NOD2 NLRP3
2
Show member pathways
13.2 TNFRSF1B TNFRSF1A NOD2 IL1RN IL1RL2 IL1B
3
Show member pathways
12.88 TNFRSF1A NOD2 NLRP3 NLRP12 NLRC4 IL1B
4
Show member pathways
12.43 TNFRSF1B TNFRSF1A IL1B CASP1
5 12.41 TNFRSF1B TNFRSF1A IL1RN IL1B
6
Show member pathways
12.15 NOD2 IL1RN IL1B CASP1
7 12.13 TNFRSF1A NLRP3 IL1B CASP1
8 12.11 TNFRSF1A STING1 NLRP3 NLRC4 IL1B CASP1
9
Show member pathways
12.02 TNFRSF1A NLRP3 IL1B CASP1
10 11.87 STING1 PSTPIP1 NOD2 NLRP3 NLRP12 NLRC4
11
Show member pathways
11.82 TNFRSF1B TNFRSF1A CASP1
12 11.81 NLRP3 MEFV IL1B CASP1
13 11.76 TNFRSF1A IL1B CARD14
14 11.72 TNFRSF1B TNFRSF1A NOD2 IL1B
15
Show member pathways
11.69 PSTPIP1 NOD2 NLRP3 NLRC4 MEFV CASP1
16 11.65 NLRC4 IL1B CASP1
17 11.61 NLRP3 IL1B CASP1
18 11.43 NLRC4 IL1B CASP1
19 11.31 TNFRSF1B TNFRSF1A IL1RN IL1B
20 10.78 NOD2 NLRP3 NLRP12 NLRC4 MEFV IL1B
21 10.36 IL1B CASP1

GO Terms for Mevalonic Aciduria

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.1 STING1 PSTPIP1 NOD2 NLRP3 NLRP12 NLRC4
2 autophagosome GO:0005776 9.5 STING1 MEFV IL1B
3 NLRP3 inflammasome complex GO:0072559 9.16 NLRP3 CASP1
4 IPAF inflammasome complex GO:0072557 8.96 NLRC4 CASP1
5 tumor necrosis factor receptor superfamily complex GO:0002947 8.62 TNFRSF1B TNFRSF1A

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

(show all 40)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.27 TNFRSF1A PSTPIP1 NLRP3 NLRP12 IL1RN IL1RL2
2 immune system process GO:0002376 10.06 STING1 PSTPIP1 NOD2 NLRP3 NLRC4 MEFV
3 apoptotic process GO:0006915 10.04 TNFRSF1B TNFRSF1A NLRP3 NLRC4 IL1B CASP1
4 innate immune response GO:0045087 9.98 STING1 PSTPIP1 NOD2 NLRP3 NLRC4 MEFV
5 regulation of apoptotic process GO:0042981 9.96 NOD2 NLRC4 CASP1 CARD14
6 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 9.88 TNFRSF1A NOD2 IL1RN IL1B CASP1
7 tumor necrosis factor-mediated signaling pathway GO:0033209 9.85 TNFRSF1B TNFRSF1A CARD14
8 cytokine-mediated signaling pathway GO:0019221 9.85 TNFRSF1B TNFRSF1A IL1RN IL1RL2 IL1B CASP1
9 positive regulation of inflammatory response GO:0050729 9.83 TNFRSF1A NLRP12 IL1B
10 interleukin-1-mediated signaling pathway GO:0070498 9.83 NOD2 IL1RN IL1RL2 IL1B
11 positive regulation of JNK cascade GO:0046330 9.82 NOD2 IL1RN IL1B
12 cellular response to mechanical stimulus GO:0071260 9.82 TNFRSF1A IL1B CASP1
13 cellular response to organic cyclic compound GO:0071407 9.81 STING1 NOD2 IL1B
14 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006919 9.81 NLRP3 NLRP12 NLRC4 CASP1
15 positive regulation of NIK/NF-kappaB signaling GO:1901224 9.8 NOD2 NLRP12 IL1B
16 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.8 NOD2 NLRP3 NLRC4 IL1B CARD14
17 cellular response to cytokine stimulus GO:0071345 9.79 NLRP12 IL1RL2 CASP1
18 positive regulation of interleukin-6 production GO:0032755 9.76 NOD2 IL1RN IL1RL2 IL1B
19 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043122 9.68 NLRP12 IL1B
20 negative regulation of cardiac muscle hypertrophy GO:0010614 9.68 TNFRSF1B TNFRSF1A
21 positive regulation of interleukin-1 beta production GO:0032731 9.67 NOD2 CASP1
22 positive regulation of membrane protein ectodomain proteolysis GO:0051044 9.67 TNFRSF1B IL1B
23 isoprenoid biosynthetic process GO:0008299 9.66 MVK HMGCR
24 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 9.65 NLRP12 NLRC4
25 regulation of inflammatory response GO:0050727 9.65 STING1 NOD2 NLRP3 IL1RL2 CASP1
26 detection of bacterium GO:0016045 9.64 NOD2 NLRC4
27 cellular response to lipopolysaccharide GO:0071222 9.63 TNFRSF1B NOD2 NLRP3 IL1RN IL1B CASP1
28 regulation of establishment of endothelial barrier GO:1903140 9.62 TNFRSF1A IL1B
29 positive regulation of interleukin-1 beta secretion GO:0050718 9.62 NOD2 NLRP3 NLRP12 CASP1
30 cellular response to peptidoglycan GO:0071224 9.61 NOD2 NLRP3
31 positive regulation of type 2 immune response GO:0002830 9.61 NOD2 NLRP3
32 interleukin-1 beta production GO:0032611 9.6 NLRP3 IL1B
33 aortic valve development GO:0003176 9.59 TNFRSF1B TNFRSF1A
34 negative regulation of extracellular matrix constituent secretion GO:0003332 9.58 TNFRSF1B TNFRSF1A
35 pulmonary valve development GO:0003177 9.57 TNFRSF1B TNFRSF1A
36 cytokine secretion involved in immune response GO:0002374 9.56 NOD2 NLRP3
37 positive regulation of apoptotic process involved in morphogenesis GO:1902339 9.55 TNFRSF1B TNFRSF1A
38 detection of biotic stimulus GO:0009595 9.54 NOD2 NLRP3
39 negative regulation of inflammatory response GO:0050728 9.43 TNFRSF1B TNFRSF1A NLRP3 NLRP12 MVK MEFV
40 inflammatory response GO:0006954 9.28 TNFRSF1B TNFRSF1A PSTPIP1 NLRP3 NLRC4 MEFV

Molecular functions related to Mevalonic Aciduria according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.19 TNFRSF1B TNFRSF1A STING1 PSTPIP1 NOD2 NLRP3
2 ATP binding GO:0005524 9.98 NOD2 NLRP3 NLRP12 NLRC4 MVK MMAB
3 identical protein binding GO:0042802 9.7 STING1 PSTPIP1 NLRP3 NLRC4 MVK MEFV
4 peptidoglycan binding GO:0042834 9.46 NOD2 NLRP3
5 cysteine-type endopeptidase activator activity involved in apoptotic process GO:0008656 9.4 NLRP12 CASP1
6 interleukin-1 receptor binding GO:0005149 9.37 IL1RN IL1B
7 tumor necrosis factor-activated receptor activity GO:0005031 9.32 TNFRSF1B TNFRSF1A
8 tumor necrosis factor binding GO:0043120 8.96 TNFRSF1B TNFRSF1A
9 CARD domain binding GO:0050700 8.8 NOD2 CASP1 CARD14

Sources for Mevalonic Aciduria

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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