Permanent neonatal diabetes mellitus – the importance of diabetes differential diagnosis in neonates and infants

Authors

  • Oscar Rubio-Cabezas,

    1. Institute of Biomedical and Clinical Science, Peninsula Medical School, Universities of Exeter & Plymouth, Exeter, UK
    2. Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
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  • Tomasz Klupa,

    1. Department of Metabolic Diseases, Medical College, Jagiellonian University, Krakow
    2. University Hospital, Krakow, Poland
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  • Maciej T. Malecki,

    1. Department of Metabolic Diseases, Medical College, Jagiellonian University, Krakow
    2. University Hospital, Krakow, Poland
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  • CEED3 Consortium


Maciej T. Malecki, MD, PhD, Department of Metabolic Diseases, Jagiellonian University, Medical College, 15 Kopernika Street, 31-501 Krakow, Poland. Tel.: (+48) 421 39 72; fax: (+48) 421 97 86 ; e-mail: malecki_malecki@yahoo.com; mmalecki@cm-uj.krakow.pl

Abstract

Eur J Clin Invest 2011; 41 (3): 323–333

Abstract

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.

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