Who should have genetic testing for maturity-onset diabetes of the young?
Article first published online: 7 SEP 2011
© 2011 Blackwell Publishing Ltd
Volume 75, Issue 4, pages 422–426, October 2011
How to Cite
Naylor, R. and Philipson, L. H. (2011), Who should have genetic testing for maturity-onset diabetes of the young?. Clinical Endocrinology, 75: 422–426. doi: 10.1111/j.1365-2265.2011.04049.x
- Issue published online: 7 SEP 2011
- Article first published online: 7 SEP 2011
- Accepted manuscript online: 19 MAR 2011 07:45AM EST
- (Received 26 January 2011; returned for revision 8 February 2011; finally revised 14 March 2011; accepted 14 March 2011)
Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic disorders characterized by autosomal dominant inheritance of young-onset, non-insulin-dependent diabetes. The genes involved are important in beta cell development, function and regulation and lead to disorders in glucose sensing and insulin secretion. Heterozygous GCK mutations cause impaired glucokinase activity resulting in stable, mild hyperglycaemia that rarely requires treatment. HNF1A mutations cause a progressive insulin secretory defect that is sensitive to sulphonylureas, most often resulting in improved glycaemic control compared with other diabetes treatment. MODY owing to mutations in the HNF4A gene results in a similar phenotype, including sensitivity to sulphonylurea treatment. HNF1B mutations most frequently cause developmental renal disease (particularly renal cysts) but may also cause MODY in isolation or may cause the renal cysts and diabetes syndrome (RCAD syndrome). Mutations in NEUROD1, PDX1 (IPF1), CEL and INS are rare causes of MODY. MODY is often misdiagnosed as type 1 or type 2 diabetes. However, a correct genetic diagnosis impacts treatment and identifies at-risk family members. Thus, it is important to consider a diagnosis of MODY in appropriate individuals and to pursue genetic testing to establish a molecular diagnosis.