Hepatocyte nuclear factor 1β maturity-onset diabetes of the young in a Chinese child presenting with hyperglycemic hyperosmolar state

Excerpt

Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes, of which 13 subtypes have been reported to date. Hepatocyte nuclear factor 1β maturity-onset diabetes of the young (HNF1β-MODY) was previously called MODY type 5 (MODY5) diabetes or the renal cysts and diabetes syndrome (RCAD). It is a syndrome that results from heterozygous molecular mutations of the hepatocyte nuclear factor 1-beta (HNF1β) gene. HNF1β is located on chromosome 17q12 and comprises of nine coding exons. It is a member of the homeodomain-containing superfamily of genes that encodes a widely distributed Pit-1/Oct-1/Unc-86 (POU) transcription factor which has a major role in endodermal development. HNF1β-MODY is characterized by early onset form of diabetes, severe abnormalities of the kidney as well as pancreas hypoplasia, liver dysfunction and genital tract malformation. Renal manifestations which are prevalent with HNF1β mutation carriers include; hypoplastic glomerulocystic kidney disease, cystic renal dysplasia, solitary functioning kidney, horseshoe kidney, and oligomeganephronia. The hyperosmolar hyperglycemic state (HHS) is the most serious acute hyperglycemic emergency in diabetes, with a reported mortality 10 times higher than diabetic ketoacidosis (DKA). Most cases of HHS are seen in elderly patients with type 2 diabetes. It is extremely uncommon for a patient with MODY to initially present with HHS. It is also rare for HHS to be the initial presentation of childhood diabetes. Here we report the clinical characteristics in a Chinese girl presenting with HHS and a novel mutation in HNF1β, thereby expanding the spectrum of known mutations associated with HNF1β-MODY. …