ABCC8 haploinsufficiency in a mother-daughter pair with young-onset diabetes with and without neonatal hypoglycemia.

The ATP-binding cassette transporter subfamily C member 8 (ABCC8) regulates insulin secretion from β-cells. Loss- and gain-of-function variants of ABCC8 have been implicated in neonatal hyperinsulinemic hypoglycemia and young-onset diabetes, respectively. Although some patients with ABCC8 variants have been reported to exhibit both neonatal hypoglycemia and young-onset diabetes, the molecular and clinical characteristics of this atypical phenotype remain unknown. Here, we report a girl and her mother with a heterozygous truncating ABCC8 variant (c.2857C>T, p.Gln953Ter). The girl showed a large birth weight and mild neonatal hypoglycemia. She developed diabetes at 10 yrs of age and was treated with insulin. Her mother had a normal birth weight and no history of hypoglycemia. The mother had gestational diabetes during each of her five pregnancies. She was subsequently diagnosed with diabetes at 35 yrs of age and treated with oral hypoglycemic agents. This study provides evidence that ABCC8 haploinsufficiency leads to variable phenotypes in a family. These phenotypes include the hyperinsulinemia-remission-diabetes sequence and young-onset diabetes without apparent neonatal hyperinsulinemia.