Expanding the clinical spectrum of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency with Turkish cases harboring novel HMGCS2 gene mutations and literature review

Am J Med Genet A. 2020 Jul;182(7):1608-1614. doi: 10.1002/ajmg.a.61590. Epub 2020 Apr 7.

Abstract

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is a very rare autosomal recessive inborn error of ketone body synthesis and presents with hypoketotic hypoglycemia, metabolic acidosis, lethargy, encephalopathy, and hepatomegaly with fatty liver precipitated by catabolic stress. We report acute presentation of two patients from unrelated two families with novel homozygous c.862C>T and c.725-2A>C mutations, respectively, in HMGCS2 gene. Affected patients had severe hypoketotic hypoglycemia, lethargy, encephalopathy, severe metabolic and lactic acidosis and hepatomegaly after infections. Surprisingly, molecular screening of the second family showed more affected patients without clinical findings. These cases expand the clinic spectrum of this extremely rare disease.

Keywords: 3-hydroxy-3-methylglutaryl-CoA synthase deficiency; HMG-CoA synthase deficiency; HMGCS2; encephalopathy; hypoglycemia.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Acidosis / genetics
  • Adolescent
  • Child, Preschool
  • Female
  • Hepatomegaly / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Synthase / deficiency*
  • Hydroxymethylglutaryl-CoA Synthase / genetics
  • Hypoglycemia / etiology*
  • Hypoglycemia / genetics
  • Infant
  • Lethargy / etiology
  • Male
  • Metabolism, Inborn Errors / etiology*
  • Metabolism, Inborn Errors / genetics
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / genetics
  • Mutation*
  • Turkey

Substances

  • HMGCS2 protein, human
  • Hydroxymethylglutaryl-CoA Synthase

Supplementary concepts

  • 3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency