U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from Gene

3-hydroxy-3-methylglutaryl-CoA synthase deficiency(HMGCS2D)

MedGen UID:
414399
•Concept ID:
C2751532
•
Disease or Syndrome
Synonyms: 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency; HMG-CoA synthase-2 deficiency; HMGCS2 DEFICIENCY; HMGCS2D; mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency; MITOCHONDRIAL HMG-CoA SYNTHASE DEFICIENCY
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): HMGCS2 (1p12)
 
Monarch Initiative: MONDO:0011614
OMIM®: 605911
Orphanet: ORPHA35701

Definition

Mitochondrial HMG-CoA synthase deficiency (HMGCS2D) 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). [from OMIM]

Clinical features

From HPO
Diarrhea
MedGen UID:
8360
•Concept ID:
C0011991
•
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
See: Feature record | Search on this feature
Hepatomegaly
MedGen UID:
42428
•Concept ID:
C0019209
•
Finding
Abnormally increased size of the liver.
See: Feature record | Search on this feature
Vomiting
MedGen UID:
12124
•Concept ID:
C0042963
•
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
See: Feature record | Search on this feature
Hypoglycemic coma
MedGen UID:
5710
•Concept ID:
C0020617
•
Disease or Syndrome
Coma induced by low blood sugar.
See: Feature record | Search on this feature
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
•Concept ID:
C0151904
•
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
See: Feature record | Search on this feature
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
•Concept ID:
C0151905
•
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
See: Feature record | Search on this feature
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
•Concept ID:
C4477095
•
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
See: Feature record | Search on this feature
Show allHide all

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV3-hydroxy-3-methylglutaryl-CoA synthase deficiency
Follow this link to review classifications for 3-hydroxy-3-methylglutaryl-CoA synthase deficiency in Orphanet.

Professional guidelines

PubMed

Genotype-based databases for variants causing rare diseases.
Lanthaler B, Wieser S, Deutschmann A, Schossig A, Fauth C, Zschocke J, Witsch-Baumgartner M
Gene 2014 Oct 15;550(1):136-40. Epub 2014 Aug 8 doi: 10.1016/j.gene.2014.08.016. PMID: 25111118

Recent clinical studies

Etiology

Clinical and biochemical features of fatty acid oxidation disorders.
Rinaldo P, Raymond K, al-Odaib A, Bennett MJ
Curr Opin Pediatr 1998 Dec;10(6):615-21. doi: 10.1097/00008480-199810060-00014. PMID: 9848022

Diagnosis

Clinical, biochemical, molecular and therapeutic characteristics of four new patients of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency.
Wang Q, Yang YL, Liu M, Chen JJ, Li XQ, Cao BY, Gong CX
Clin Chim Acta 2020 Oct;509:83-90. Epub 2020 May 26 doi: 10.1016/j.cca.2020.04.004. PMID: 32470406
Human Mitochondrial HMG-CoA Synthase Deficiency: Role of Enzyme Dimerization Surface and Characterization of Three New Patients.
Puisac B, Marcos-Alcalde I, Hernández-Marcos M, Tobajas Morlana P, Levtova A, Schwahn BC, DeLaet C, Lace B, Gómez-Puertas P, Pié J
Int J Mol Sci 2018 Mar 28;19(4) doi: 10.3390/ijms19041010. PMID: 29597274Free PMC Article
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: urinary organic acid profiles and expanded spectrum of mutations.
Pitt JJ, Peters H, Boneh A, Yaplito-Lee J, Wieser S, Hinderhofer K, Johnson D, Zschocke J
J Inherit Metab Dis 2015 May;38(3):459-66. Epub 2014 Dec 16 doi: 10.1007/s10545-014-9801-9. PMID: 25511235
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients.
Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A, Boukaftane Y, Ashmarina L, Wang S, Miziorko H, Mitchell GA
Pediatr Res 2001 Mar;49(3):326-31. doi: 10.1203/00006450-200103000-00005. PMID: 11228257
Clinical and biochemical features of fatty acid oxidation disorders.
Rinaldo P, Raymond K, al-Odaib A, Bennett MJ
Curr Opin Pediatr 1998 Dec;10(6):615-21. doi: 10.1097/00008480-199810060-00014. PMID: 9848022

Prognosis

Severe clinical manifestation of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency associated with two novel mutations: a case report.
Liu H, Miao JK, Yu CW, Wan KX, Zhang J, Yuan ZJ, Yang J, Wang DJ, Zeng Y, Zou L
BMC Pediatr 2019 Oct 9;19(1):344. doi: 10.1186/s12887-019-1747-5. PMID: 31597564Free PMC Article
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: urinary organic acid profiles and expanded spectrum of mutations.
Pitt JJ, Peters H, Boneh A, Yaplito-Lee J, Wieser S, Hinderhofer K, Johnson D, Zschocke J
J Inherit Metab Dis 2015 May;38(3):459-66. Epub 2014 Dec 16 doi: 10.1007/s10545-014-9801-9. PMID: 25511235
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients.
Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A, Boukaftane Y, Ashmarina L, Wang S, Miziorko H, Mitchell GA
Pediatr Res 2001 Mar;49(3):326-31. doi: 10.1203/00006450-200103000-00005. PMID: 11228257

Clinical prediction guides

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: urinary organic acid profiles and expanded spectrum of mutations.
Pitt JJ, Peters H, Boneh A, Yaplito-Lee J, Wieser S, Hinderhofer K, Johnson D, Zschocke J
J Inherit Metab Dis 2015 May;38(3):459-66. Epub 2014 Dec 16 doi: 10.1007/s10545-014-9801-9. PMID: 25511235
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: clinical course and description of causal mutations in two patients.
Bouchard L, Robert MF, Vinarov D, Stanley CA, Thompson GN, Morris A, Leonard JV, Quant P, Hsu BY, Boneh A, Boukaftane Y, Ashmarina L, Wang S, Miziorko H, Mitchell GA
Pediatr Res 2001 Mar;49(3):326-31. doi: 10.1203/00006450-200103000-00005. PMID: 11228257

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed
    • PubMed (OMIM)
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...