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

Mustafa Kılıç, Sevil Dorum, Ali Topak, Mutlu U Yazıcı, Fatih S Ezgu, Turgay Coskun

Journal: American journal of medical genetics. Part A 2021;182(7):1608-1614

PMID: 32259399

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.

Address: Sami Ulus Children Hospital, Metabolism Unit, Ankara, Turkey.; Department of Pediatrics, Metabolism Unit, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey.; Medical Genetic Unit, Yuksek Ihtisas Training and Research Hospital, Bursa, Turkey.; Sami Ulus Children Hospital, Intensive Care Unit, Ankara, Turkey.; Department of Pediatrics, Metabolism Unit, Gazi University, Ankara, Turkey.; Department of Pediatrics, Metabolism Unit, Hacettepe University, Ankara, Turkey.

DOI: 10.1002/ajmg.a.61590

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MeSH Terms: Acidosis, Adolescent, Child, Preschool, Female, Hepatomegaly, Humans, Hydroxymethylglutaryl-CoA Synthase, Hypoglycemia, Infant, Lethargy, Male, Metabolism, Inborn Errors, Mitochondrial Diseases, Mutation, Turkey