Siblings With Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism
JCEM case reports
Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy. Mutations in the gene for heterozygous hepatocyte nuclear transcription factor 4-alpha () account for approximately 5% of cases and are inherited in an autosomal dominant fashion or arise as de novo mutations. This case describes a unique presentation of parental gonadal, or germline, mosaicism as the suspected inheritance pattern for siblings with congenital hyperinsulinism caused by mutations. Two siblings presented with hypoglycemia in the first hours of life and were subsequently confirmed to have hyperinsulinism. In each patient, glycemic control was achieved at relatively low doses of diazoxide. Both siblings tested positive for the same mutation, whereas the parents tested negative for mutations. Gonadal, or germline, mosaicism became the presumed leading diagnosis, given 2 unaffected parents with 2 children with congenital hyperinsulinism. The older sibling demonstrated additional clinical features of liver disease and renal Fanconi syndrome, both of which are associated with mutations. Genetic testing plays an important role in the diagnosis and management of congenital hyperinsulinism. mutations may arise by a range of mechanisms, including gonadal, or germline, mosaicism. mutations have phenotypic variance that may affect multiple organ systems at any age.
Wolschendorf R, Eimicke T, Swartz J. Siblings With HNF4A Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism. JCEM Case Rep. 2023;1(4):luad089. Published 2023 Aug 14. doi:10.1210/jcemcr/luad089