A new case of M/SCHAD deficiency: the contribution of metabolic findings in directing the definitive genetic diagnosis for an optimal management

Congenital hyperinsulinemic hypoglycemia (CHH) is a rare metabolic disease (prevalence <1/1,000,000) characterized by persistent hypoglycemia and inappropriate secretion of insulin often in neonatal period and infancy. Early diagnosis and management of patients with CHH are important to avoid brain damage. Recent advances in genetics have showed that CHH is due to mutations in twelve genes: ABCC8, KCNJ11, GCK, GLUD1, HADH, SLC16A1, UCP2, HNF1A, HNF4A, HK1, PGM1 and CACNA1D. The HADH gene codifies the medium and short chain 3-hydroxyacyl-CoA dehydrogenase (M./SCHAD), a mitochondrial matrix enzyme which catalyzes the penultimate reaction in the beta-oxidation of medium and short-chain fatty acids, specifically the conversion of medium- and short-chain L-3-hydroxyacyl-CoA to corresponding 3-ketoacyl-CoA. Mutations in this gene result in a recessive form of CHH, with a good diazoxide responsivity and, occasionally, an abnormal urinary organic acid and plasma acylcarnitine's profile. Herein, we describe a new case of CHH due to M/SCHAD deficiency, highlighting the importance of metabolic findings to lead genetic testing and clinical management.