A case of transient neonatal diabetes due to a novel mutation in ABCC8

Neonatal diabetes mellitus (NDM), characterized by hyperglycemia and the need for insulin treatment within the first 6 mo of life, is a rare monogenic form of diabetes with an estimated incidence of 1 in 90,000 neonates (1). Approximately half of NDM cases are transient and resolve at a median age of 3 mo (transient NMD: TNDM), while the remaining cases develop into a permanent form of diabetes (permanent NDM: PNDM; MIM # 606176). Adult onset non-autoimmune diabetes occurs in a significant number of patients with TNDM (2). Most cases of TNDM (approximately 70%) are caused by abnormalities in chromosome 6q24, including paternal duplications, paternal uniparental isodisomy, and loss of methylation. In a few patients, activating mutations in the genes, which encode the two subunits of the β-cell ATP-sensitive potassium channel, i.e. ABCC8 and KCNJ11, have been reported to be associated with TNDM. Interestingly, recent studies have shown that familial analysis of TNMD with ABCC8 mutations revealed that their family members with adult onset non-autoimmune diabetes also have the same mutations (3). Here, we present a Japanese case with TNDM harboring a novel p.Glu350Asp mutation in ABCC8. Familial analysis revealed that his non-symptomatic sister and mother, other family members with adult-onset diabetes without neonatal episodes of hyperglycemia, also possessed the same mutation.