Differential diagnosis of type 1 diabetes: which genetic syndromes need to be considered?

Abstract

Recently it has become apparent that not all diabetes presenting in childhood is type 1. Increasingly type 2 diabetes, secondary diabetes, maturity onset diabetes of the young, and rare syndromic forms of diabetes such as Wolfram syndrome and Alstrom syndrome have been identified in children. Although individually rare, collectively they make up about 5% of children seen in diabetes clinics. The importance of these syndromes for children lies in the recognition of treatable complications, and for their parents, the possibility of genetic counselling. The scientific importance is enormous as they are experiments of nature that reveal basic mechanisms of insulin and glucose metabolism. We are now able to offer mutation analysis to correlate the clinical pattern to the genotype, and seek novel therapeutic approaches based on the developing knowledge of gene and protein functions. This review focuses on monogenic syndromes of diabetes, particularly where significant advances have been made in our understanding recently. Neonatal diabetes is a specialist field in its own right and is not included, except to discuss Kir6.2 diabetes which may develop in infancy. This review is written for the paediatric diabetes specialist and aims to provide information on the clinical features, natural history, genetics and management of children with diabetes as part of a syndrome. Finally there is information on useful investigations to aid diagnosis.