Clinical and Laboratory ObservationHyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene
Section snippets
Clinical Case History
This child was born to consanguineous first cousin parents, with a birth weight of 3.1 kg. At 4 months of age he presented with hypoglycemia and seizures. Investigations showed an increased glucose clearance rate (7 mg/kg per minute) and a biochemical picture consistent with hyperinsulinemic hypo–fatty acidemic hypoketotic hypoglycemia. This patient responded to 5 mg/kg per day diazoxide and 7.5 mg/kg per day chlorothiazide.
Measurement of 3-Hydroxyacyl-CoA Dehydrogenase Activity
Short-, medium-, and long-chain 3-hydroxyacyl-CoA dehydrogenase
Results
The results of the diagnostic fast were similar to the first patient we described.5 During one fast with a blood glucose level of 1.9 mmol/L, insulin level was <1 mU/L and NEFA (1.49 mmol/L) and 3-hydroxybutyrtae (0.53 mmol/L) were elevated. During a second fast with a blood glucose level of 2.9 mmol/L, the insulin level was elevated at 3.0 mU/L, with suppressed NEFA (0.50 mmol/L) and ketones (<0.05 mmol/L).
Hydroxybutyrylcarnitine was persistently elevated (0.70 to 1.69 μmol/L). Urine organic
Discussion
This is the third reported case of a mutation in the SCHAD gene in a patient with hyperinsulinism. All reported cases have presented with increased 3-hydroxyglutarate in urine and hydroxybutyrylcarnitine in blood, diagnostically useful markers for SCHAD deficiency. The clinical presentation is heterogeneous, with either mild late onset hypoglycaemia or severe neonatal hypoglycaemia.5, 7
The mechanism of how a defect in SCHAD leads to dysregulated insulin secretion is unclear at present. In the
References (11)
The ins and outs of fatty acids on the pancreatic beta cell
Trends Endocrinol Metab
(2003)Control of mitochondrial b-oxidation flux
Prog Lipid Res
(2002)- et al.
The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids
J Biol Chem
(2003) Triggering and amplifying pathways of regulation of insulin secretion by glucose
Diabetes
(2000)- et al.
Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: Role in beta-cell adaptation and failure in the etiology of diabetes
Diabetes
(2002)
Cited by (66)
Hypoglycemia in the Newborn and Infant
2020, Sperling Pediatric Endocrinology: Expert Consult - Online and PrintPathophysiology of Neonatal Hypoglycemia
2017, Fetal and Neonatal Physiology, 2-Volume SetHypoglycemia
2015, Genetic Diagnosis of Endocrine Disorders: Second EditionMitochondrial regulation of β-cell function: Maintaining the momentum for insulin release
2015, Molecular Aspects of MedicineHypoglycemia in the newborn and infant
2014, Pediatric Endocrinology: Fourth EditionPediatric hypoglycemia
2014, Advances in Clinical ChemistryCitation Excerpt :This enzyme is now known as hydroxyl acyl-coenzyme A dehydrogenase (HADH). The inhibition of HADH, due to a mutation in its gene, may also cause protein-induced HH [61–64]. Patients may present in the neonatal period or more commonly later in life with hypoglycemia and increased hydroxybutyrylcarnitine and urine 3-hydroxyglutarate.
Supported by the NHS Executive R & D funding (Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust).