Genetic pathogenesis, diagnosis, and treatment of short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism

Orphanet J Rare Dis. 2021 Nov 4;16(1):467. doi: 10.1186/s13023-021-02088-6.


Congenital hyperinsulinism (CHI), a major cause of persistent and recurrent hypoglycemia in infancy and childhood. Numerous pathogenic genes have been associated with 14 known genetic subtypes of CHI. Adenosine triphosphate-sensitive potassium channel hyperinsulinism (KATP-HI) is the most common and most severe subtype, accounting for 40-50% of CHI cases. Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism (SCHAD-HI) is a rare subtype that accounts for less than 1% of all CHI cases that are caused by homozygous mutations in the hydroxyacyl-coenzyme A dehydrogenase (HADH) gene. This review provided a systematic description of the genetic pathogenesis and current progress in the diagnosis and treatment of SCHAD-HI to improve our understanding of this disease.

Keywords: Congenital hyperinsulinism (CHI); Hydroxyacyl-coenzyme A dehydrogenase (HADH) gene; Hypoglycemia; Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism (SCHAD-HI).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics*
  • Child
  • Congenital Hyperinsulinism* / diagnosis
  • Congenital Hyperinsulinism* / drug therapy
  • Congenital Hyperinsulinism* / genetics
  • Homozygote
  • Humans
  • Hyperinsulinism*
  • Mutation / genetics


  • 3-Hydroxyacyl CoA Dehydrogenases
  • HSD17B10 protein, human