A recent study illustrated that the same genotype can give rise to a biphasic phenotype in the same person or a reverse phenotype in someone from the same family in monogenic cases with hyperinsulinism. The results of this study were published in Reviews in Endocrine and Metabolic Disorders.
The study aimed to describe individual or family monogenic association between hyperinsulinemic hypoglycemia (HH) and diabetes, and identify potential genotype-phenotype correlations. The systematic review of 26 studies consisted of 67 patients with this association resulting from variants in GCK, ABCC8, HNF1A OR HNF4A.
In 91% of cases, there was a family history of hypoglycemia and/or diabetes. Median age at first hypoglycemia was 24 h after birth. Diazoxide was initiated in 46 children; responsiveness was found in 91%. Median HH duration was three years, and twenty-three patients developed diabetes later; more frequently in those untreated with diazoxide. It was concluded that this link was most often inherited in an autosomal dominant manner. Some genes were associated with less severe initial hypoglycemia, shorter duration of HH, and more maternal or paternal transmission.
Since, Maturity-Onset Diabetes of the Youth (MODY) diabetes is often misdiagnosed, this phenotype association suggests annual monitoring of patients who have presented HH and during maternity to screen diabetes and optimize genetic counselling.
Perge, K., & Nicolino, M. (2022). Variable phenotypes of individual and family monogenic cases with hyperinsulinism and diabetes: a systematic review. Reviews in endocrine & metabolic disorders, 23(5), 1063–1078. https://link.springer.com/article/10.1007/s11154-022-09749-2#Sec17