Endocrine Abstracts

A 36-year-old Caucasian male was referred in November 2021 to our clinic, for investigations regarding his recent genetic diagnosis of congenital hyperinsulinism, revealed by genetic testing, performed after the birth of couple’s second child presenting with recurrent hypoglycemia.The female newborn diagnosed with fetal macrosomia (birth at 38 weeks, 4.3 kg), required follow-up and further examinations.A massive parallel sequencing on panel of 4867 genes using Roche platform, performed on the entire family, revealed the presence in the heterozygous state of the variant c.4432G>A, p.Gly1478Arg in the ABCC8 gene in the newborn, her father and the couple’s first child, born in 2018 (3.6 kg at 36 weeks), which inherited the variant, but had no suspicious event of hypoglycemia.In our patient, the condition is transmitted in the autosomal dominant mode.Each child of a carrier individual has a 50% risk of inheriting the anomaly. However, the expressivity is variable and the penetrance incomplete, therefore the severity of the phenotype cannot be predicted.Venous blood sample showed non-fasting sugar level at 62 mg/dl(3.4 mmol/l) with inappropriate normal value of C-Peptide(0.954 nmol/l) and insulin(92.9 pmol/l).7-day continuous glucose monitoring (CGM) with Dexcom G5® Mobile CGM System, highlighted several hypoglycemic events, confirmed by fingerstick measurement, going as low as 45 mg/dl (2.5 mmol/l) linked mostly to meals, occasional alcohol consumption or after a 5-hour fasting period. Going backward in time, in the light of this new medical information, the patient could relate with his condition several unexplained symptoms that he presented over time, since childhood, as mild headaches and extreme hunger.Regarding the treatment, the simplest strategy is to eat several small low-carbohydrate meals daily. If not sufficient, further treatment is based on Diazoxide, a potassium channel agonist which inhibits insulin secretion in some forms of congenital hyperinsulinism by stimulating the opening of KATP channels leading to hyperpolarization of the β-cell membrane and inhibiting insulin secretion or Octreotide, a somatostatin analog that acts to suppress insulin release downstream of the KATP channel.The patient was placed on a low-carb meal regimen with successful prevention of hypoglycemic events.The understanding of the genetic basis of familial hyperinsulinism should borne in mind that certain patients with hypoglycemia might present genetic forms with late-onset (or late diagnosis), such as congenital hyperinsulinism.Mild hypoglycemia in an adult can be easily missed, but the underlying cause can be rare with important further implications for the patient and his offspring.