Childhood Onset of Sulfonylurea Responsive Neonatal Diabetes Due to a Novel Homozygous Autosomal Recessive Mutation in the ABCC8 Gene which was Presumed to be Type 1B Diabetes Before Genetic Analysis

ABSTRACT Objective: To describe an atypical childhood onset presentation of sulfonylurea-responsive neonatal diabetes mellitus (NDM) resulting from the unusually late expression of a homozygous, novel ABCC8 gene mutation. Onset was at 9 years of age and was initially misdiagnosed as being type 1B diabetes, with subsequent treatment as insulin-dependent diabetes before a genetic analysis was performed. Methods: Genetic screening of the individual and her family was conducted due to history of her youngest brother having classic NDM with onset at 2 months of age, later confirmed to be due to an identical homozygous mutation. Results: Both siblings were successfully shifted to treatment with an oral sulfonylurea following genetic diagnosis. Conclusion: We report the first case of a childhood onset, autosomal recessive ABCC8 mutation in a homozygous state presenting as type 1B diabetes. Current recommendations are to perform genetic screening for NDM only when the age of onset is less than 1 year. Our case highlights that apparently insulin-dependent diabetes that is actually due to ABCC8 mutation can present later in childhood, with an onset even as late as 9 years, and thus can be easily confused with childhood onset type 1B diabetes, even in the homozygous state. Genetic analysis and subsequent transfer to sulfonylurea therapy if responsive can significantly change lifelong disease management in such patients. Abbreviations: ABCC8 = ATP binding cassette transporter subfamily C member 8 BMI = body mass index DM = diabetes mellitus INS = insulin gene KATP = ATP-sensitive potassium channel KCNJ11 = potassium channel J11 Kir6.2 = inward rectifier K+ channel MMTT = mixed meal tolerance test NDM = neonatal diabetes mellitus PNDM = permanent neonatal diabetes mellitus TNDM = transient neonatal diabetes mellitus