Permanent neonatal diabetes mellitus – the importance of diabetes differential diagnosis in neonates and infants
Article first published online: 4 NOV 2010
© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation
European Journal of Clinical Investigation
Volume 41, Issue 3, pages 323–333, March 2011
How to Cite
Rubio-Cabezas, O., Klupa, T., Malecki, M. T. and CEED3 Consortium (2011), Permanent neonatal diabetes mellitus – the importance of diabetes differential diagnosis in neonates and infants. European Journal of Clinical Investigation, 41: 323–333. doi: 10.1111/j.1365-2362.2010.02409.x
- Issue published online: 8 FEB 2011
- Article first published online: 4 NOV 2010
- Received 1 July 2010; accepted 21 September 2010
- Differential diagnosis;
- monogenic disease;
- neonatal diabetes
Eur J Clin Invest 2011; 41 (3): 323–333
Background The differential diagnosis of various types and forms of diabetes is of great practical importance. This is particularly true for monogenic disease forms, where some spectacular applications of pharmacogenetics have recently been described.
Design For many years the distinct character of diabetes diagnosed in the first weeks and months of life remained unnoticed. The results of the search for type 1 diabetes-related autoantibodies, description of the HLA haplotypes distribution and analysis of clinical features in patients diagnosed in the first 6 months of life provided the initial evidence that the etiology of their disease might be different from that of autoimmune diabetes.
Results Over the last decade, mutations in about a dozen of genes have been linked to the development of Permanent Neonatal Diabetes Mellitus (PNDM). The most frequent causes of PNDM are heterozygous mutations in the KCNJ11, INS and ABCC8 genes. Although PNDM is a rare phenomenon (one case in about 200 000 live births), this discovery has had a large impact on clinical practice as most carriers of KCNJ11 and ABCC8 gene mutations have been switched from insulin to oral sulphonylureas with an improvement in glycemic control. In this review we summarize the practical aspects of diabetes differential diagnosis in neonates and infants.
Conclusions Genetic testing should be advised in all subjects with PNDM as it may influence medical care in subjects with these monogenic forms of early onset diabetes.