MCID: 3HY011
MIFTS: 23

3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

MalaCards integrated aliases for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

Name: 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency 57 75
Mitochondrial Hmg-Coa Synthase Deficiency 57 75
Hmg-Coa Synthase-2 Deficiency 57 13
Hmg-Coa Synthase Deficiency 59 75
Hmgcs2 Deficiency 57 75
Hmgcs2d 57 75
Mitochondrial 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Deficiency 75
3-Hydroxy-3-Methylglutaryl-Coa Synthase Deficiency, Type 2 40
3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Deficiency 73
3-Hydroxy-3-Methylglutaryl-Coa Synthase Deficiency 59
Hmg-Coa Synthase Deficiency 37
Hmgcs Deficiency 75

Characteristics:

Orphanet epidemiological data:

59
3-hydroxy-3-methylglutaryl-coa synthase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
diagnosis is difficult outside fasting because biochemical analyses give normal results and enzyme studies can only be performed in biopsied liver


HPO:

32
3-hydroxy-3-methylglutaryl-coa synthase-2 deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


External Ids:

OMIM 57 605911
Orphanet 59 ORPHA35701
ICD10 via Orphanet 34 E71.3
UMLS via Orphanet 74 C2751532
MedGen 42 C2751532
KEGG 37 H01123
UMLS 73 C2751532

Summaries for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

OMIM : 57 Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting (summary by Aledo et al., 2006). (605911)

MalaCards based summary : 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency, is also known as mitochondrial hmg-coa synthase deficiency, and has symptoms including diarrhea and vomiting. An important gene associated with 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency is HMGCS2 (3-Hydroxy-3-Methylglutaryl-CoA Synthase 2), and among its related pathways/superpathways are Synthesis and degradation of ketone bodies and Valine, leucine and isoleucine degradation. Affiliated tissues include liver, and related phenotypes are seizures and hypoglycemia

UniProtKB/Swiss-Prot : 75 3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency: A metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.

Related Diseases for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Symptoms & Phenotypes for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Symptoms via clinical synopsis from OMIM:

57
Abdomen Liver:
hepatomegaly
fatty infiltration
hmg-coa synthase activity approximately 10% of normal

Metabolic Features:
hypoketotic hypoglycemia when fasting

Abdomen Gastrointestinal:
gastroenteritis
vomiting
diarrhea
poor food intake

Laboratory Abnormalities:
highly elevated free fatty acids


Clinical features from OMIM:

605911

Human phenotypes related to 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

59 32 (show all 6)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 hypoglycemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001943
3 abnormality of metabolism/homeostasis 59 Very frequent (99-80%)
4 vomiting 32 HP:0002013
5 diarrhea 32 HP:0002014
6 hepatomegaly 32 HP:0002240

UMLS symptoms related to 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:


diarrhea, vomiting

Drugs & Therapeutics for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Search Clinical Trials , NIH Clinical Center for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Genetic Tests for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Anatomical Context for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

MalaCards organs/tissues related to 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

41
Liver

Publications for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Articles related to 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

# Title Authors Year
1
New case of mitochondrial HMG-CoA synthase deficiency. Functional analysis of eight mutations. ( 23751782 )
2013
2
Mitochondrial HMG-CoA synthase deficiency: identification of two further patients carrying two novel mutations. ( 12647205 )
2003
3
The diagnosis of mitochondrial HMG-CoA synthase deficiency. ( 12072887 )
2002
4
Genetic basis of mitochondrial HMG-CoA synthase deficiency. ( 11479731 )
2001

Variations for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

UniProtKB/Swiss-Prot genetic disease variations for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 HMGCS2 p.Phe174Leu VAR_032711 rs137852636
2 HMGCS2 p.Val54Met VAR_032757 rs28937320
3 HMGCS2 p.Tyr167Cys VAR_032758 rs137852640
4 HMGCS2 p.Gly212Arg VAR_032759 rs137852638
5 HMGCS2 p.Arg500His VAR_032760 rs137852639

ClinVar genetic disease variations for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency:

6
(show top 50) (show all 68)
# Gene Variation Type Significance SNP ID Assembly Location
1 HMGCS2 NM_001166107.1(HMGCS2): c.520T> C (p.Phe174Leu) single nucleotide variant Pathogenic rs137852636 GRCh37 Chromosome 1, 120306834: 120306834
2 HMGCS2 NM_001166107.1(HMGCS2): c.520T> C (p.Phe174Leu) single nucleotide variant Pathogenic rs137852636 GRCh38 Chromosome 1, 119764211: 119764211
3 HMGCS2 NM_005518.3(HMGCS2): c.634G> A (p.Gly212Arg) single nucleotide variant Pathogenic/Likely pathogenic rs137852638 GRCh37 Chromosome 1, 120302538: 120302538
4 HMGCS2 NM_005518.3(HMGCS2): c.634G> A (p.Gly212Arg) single nucleotide variant Pathogenic/Likely pathogenic rs137852638 GRCh38 Chromosome 1, 119759915: 119759915
5 HMGCS2 NM_001166107.1(HMGCS2): c.1373G> A (p.Arg458His) single nucleotide variant Pathogenic rs137852639 GRCh37 Chromosome 1, 120293453: 120293453
6 HMGCS2 NM_001166107.1(HMGCS2): c.1373G> A (p.Arg458His) single nucleotide variant Pathogenic rs137852639 GRCh38 Chromosome 1, 119750830: 119750830
7 HMGCS2 NM_001166107.1(HMGCS2): c.160G> A (p.Val54Met) single nucleotide variant Pathogenic rs28937320 GRCh37 Chromosome 1, 120307194: 120307194
8 HMGCS2 NM_001166107.1(HMGCS2): c.160G> A (p.Val54Met) single nucleotide variant Pathogenic rs28937320 GRCh38 Chromosome 1, 119764571: 119764571
9 HMGCS2 NM_001166107.1(HMGCS2): c.500A> G (p.Tyr167Cys) single nucleotide variant Pathogenic rs137852640 GRCh37 Chromosome 1, 120306854: 120306854
10 HMGCS2 NM_001166107.1(HMGCS2): c.500A> G (p.Tyr167Cys) single nucleotide variant Pathogenic rs137852640 GRCh38 Chromosome 1, 119764231: 119764231
11 HMGCS2 NM_005518.3(HMGCS2): c.73C> G (p.Pro25Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs144744634 GRCh38 Chromosome 1, 119768772: 119768772
12 HMGCS2 NM_005518.3(HMGCS2): c.73C> G (p.Pro25Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs144744634 GRCh37 Chromosome 1, 120311395: 120311395
13 HMGCS2; PHGDH NM_005518.3(HMGCS2): c.*165C> T single nucleotide variant Likely benign rs138575225 GRCh37 Chromosome 1, 120291305: 120291305
14 HMGCS2; PHGDH NM_005518.3(HMGCS2): c.*165C> T single nucleotide variant Likely benign rs138575225 GRCh38 Chromosome 1, 119748682: 119748682
15 HMGCS2 NM_005518.3(HMGCS2): c.*78A> G single nucleotide variant Uncertain significance rs143718202 GRCh37 Chromosome 1, 120291392: 120291392
16 HMGCS2 NM_005518.3(HMGCS2): c.*78A> G single nucleotide variant Uncertain significance rs143718202 GRCh38 Chromosome 1, 119748769: 119748769
17 HMGCS2 NM_005518.3(HMGCS2): c.1236T> C (p.Tyr412=) single nucleotide variant Uncertain significance rs773364048 GRCh38 Chromosome 1, 119753338: 119753338
18 HMGCS2 NM_005518.3(HMGCS2): c.1236T> C (p.Tyr412=) single nucleotide variant Uncertain significance rs773364048 GRCh37 Chromosome 1, 120295961: 120295961
19 HMGCS2 NM_005518.3(HMGCS2): c.862C> A (p.Arg288=) single nucleotide variant Conflicting interpretations of pathogenicity rs142637231 GRCh38 Chromosome 1, 119757427: 119757427
20 HMGCS2 NM_005518.3(HMGCS2): c.862C> A (p.Arg288=) single nucleotide variant Conflicting interpretations of pathogenicity rs142637231 GRCh37 Chromosome 1, 120300050: 120300050
21 HMGCS2 NM_005518.3(HMGCS2): c.858C> T (p.Ser286=) single nucleotide variant Conflicting interpretations of pathogenicity rs1992376 GRCh38 Chromosome 1, 119757431: 119757431
22 HMGCS2 NM_005518.3(HMGCS2): c.858C> T (p.Ser286=) single nucleotide variant Conflicting interpretations of pathogenicity rs1992376 GRCh37 Chromosome 1, 120300054: 120300054
23 HMGCS2 NM_005518.3(HMGCS2): c.275G> A (p.Arg92His) single nucleotide variant Uncertain significance rs144921290 GRCh38 Chromosome 1, 119764456: 119764456
24 HMGCS2 NM_005518.3(HMGCS2): c.275G> A (p.Arg92His) single nucleotide variant Uncertain significance rs144921290 GRCh37 Chromosome 1, 120307079: 120307079
25 HMGCS2 NM_005518.3(HMGCS2): c.26A> G (p.Lys9Arg) single nucleotide variant Uncertain significance rs144004292 GRCh38 Chromosome 1, 119768819: 119768819
26 HMGCS2 NM_005518.3(HMGCS2): c.26A> G (p.Lys9Arg) single nucleotide variant Uncertain significance rs144004292 GRCh37 Chromosome 1, 120311442: 120311442
27 HMGCS2 NM_005518.3(HMGCS2): c.1522G> A (p.Val508Ile) single nucleotide variant Uncertain significance rs76773981 GRCh37 Chromosome 1, 120293430: 120293430
28 HMGCS2 NM_005518.3(HMGCS2): c.1522G> A (p.Val508Ile) single nucleotide variant Uncertain significance rs76773981 GRCh38 Chromosome 1, 119750807: 119750807
29 HMGCS2 NM_005518.3(HMGCS2): c.1124C> G (p.Ser375Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs151328418 GRCh38 Chromosome 1, 119755490: 119755490
30 HMGCS2 NM_005518.3(HMGCS2): c.1124C> G (p.Ser375Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs151328418 GRCh37 Chromosome 1, 120298113: 120298113
31 HMGCS2 NM_005518.3(HMGCS2): c.174C> T (p.Ala58=) single nucleotide variant Conflicting interpretations of pathogenicity rs138739620 GRCh38 Chromosome 1, 119764557: 119764557
32 HMGCS2 NM_005518.3(HMGCS2): c.174C> T (p.Ala58=) single nucleotide variant Conflicting interpretations of pathogenicity rs138739620 GRCh37 Chromosome 1, 120307180: 120307180
33 HMGCS2 NM_005518.3(HMGCS2): c.-11C> T single nucleotide variant Benign/Likely benign rs2289459 GRCh38 Chromosome 1, 119768855: 119768855
34 HMGCS2 NM_005518.3(HMGCS2): c.-11C> T single nucleotide variant Benign/Likely benign rs2289459 GRCh37 Chromosome 1, 120311478: 120311478
35 HMGCS2 NM_005518.3(HMGCS2): c.-36T> G single nucleotide variant Uncertain significance rs768747562 GRCh38 Chromosome 1, 119768880: 119768880
36 HMGCS2 NM_005518.3(HMGCS2): c.-36T> G single nucleotide variant Uncertain significance rs768747562 GRCh37 Chromosome 1, 120311503: 120311503
37 HMGCS2; PHGDH NM_005518.3(HMGCS2): c.*332A> C single nucleotide variant Likely benign rs56828380 GRCh37 Chromosome 1, 120291138: 120291138
38 HMGCS2; PHGDH NM_005518.3(HMGCS2): c.*332A> C single nucleotide variant Likely benign rs56828380 GRCh38 Chromosome 1, 119748515: 119748515
39 HMGCS2 NM_005518.3(HMGCS2): c.1513C> T (p.Arg505Trp) single nucleotide variant Uncertain significance rs780044819 GRCh37 Chromosome 1, 120293439: 120293439
40 HMGCS2 NM_005518.3(HMGCS2): c.1513C> T (p.Arg505Trp) single nucleotide variant Uncertain significance rs780044819 GRCh38 Chromosome 1, 119750816: 119750816
41 HMGCS2 NM_005518.3(HMGCS2): c.621C> T (p.Pro207=) single nucleotide variant Conflicting interpretations of pathogenicity rs886045207 GRCh38 Chromosome 1, 119759928: 119759928
42 HMGCS2 NM_005518.3(HMGCS2): c.621C> T (p.Pro207=) single nucleotide variant Conflicting interpretations of pathogenicity rs886045207 GRCh37 Chromosome 1, 120302551: 120302551
43 HMGCS2 NM_005518.3(HMGCS2): c.595G> A (p.Val199Ile) single nucleotide variant Uncertain significance rs150140061 GRCh38 Chromosome 1, 119759954: 119759954
44 HMGCS2 NM_005518.3(HMGCS2): c.595G> A (p.Val199Ile) single nucleotide variant Uncertain significance rs150140061 GRCh37 Chromosome 1, 120302577: 120302577
45 HMGCS2 NM_005518.3(HMGCS2): c.*6-11_*6-8delGTTT deletion Uncertain significance rs757178898 GRCh37 Chromosome 1, 120291472: 120291475
46 HMGCS2 NM_005518.3(HMGCS2): c.*6-11_*6-8delGTTT deletion Uncertain significance rs757178898 GRCh38 Chromosome 1, 119748849: 119748852
47 HMGCS2 NM_005518.3(HMGCS2): c.1420+13T> C single nucleotide variant Uncertain significance rs771878586 GRCh37 Chromosome 1, 120295159: 120295159
48 HMGCS2 NM_005518.3(HMGCS2): c.1420+13T> C single nucleotide variant Uncertain significance rs771878586 GRCh38 Chromosome 1, 119752536: 119752536
49 HMGCS2 NM_005518.3(HMGCS2): c.1419G> A (p.Lys473=) single nucleotide variant Benign/Likely benign rs142776952 GRCh38 Chromosome 1, 119752550: 119752550
50 HMGCS2 NM_005518.3(HMGCS2): c.1419G> A (p.Lys473=) single nucleotide variant Benign/Likely benign rs142776952 GRCh37 Chromosome 1, 120295173: 120295173

Expression for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Search GEO for disease gene expression data for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency.

Pathways for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Pathways related to 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency according to KEGG:

37
# Name Kegg Source Accession
1 Synthesis and degradation of ketone bodies hsa00072
2 Valine, leucine and isoleucine degradation hsa00280
3 Butanoate metabolism hsa00650
4 Terpenoid backbone biosynthesis hsa00900

GO Terms for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

Sources for 3-Hydroxy-3-Methylglutaryl-Coa Synthase-2 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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