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Clinical, molecular, and therapeutic aspects of NDM in ten cases with diabetes in 1st 6 months of life

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Abstract

Neonatal diabetes mellitus (NDM) is defined as hyperglycemia occurring within the first 6 months of life; it may be permanent or transient. Diagnosis of NDM is vital for prognosis, genetic counseling, and treatment. The aim of this study was to study clinical, biochemical, molecular, and therapeutic aspects of diabetes presenting in the first 6 months of life. Ten cases with NDM were studied regarding perinatal and family history, clinical features and biochemical tests on admission and follow-up, HLA typing and molecular studies, and mode of therapy. Molecular studies for the common mutations associated with NDM (KCNJ11, INS, ABCC8 and methylation defects) were done using PCR amplification and gene sequencing. Ten cases developed diabetes in the first 6 months of life (three in the first 8 weeks, seven between 8 and 24 weeks). All presented with ketoacidosis, one had developmental delay with convulsions. Molecular studies revealed methylation defect in two cases, KCNJ11 in three cases, INS mutations in two cases, and no detectable defect in three cases. Insulin was stopped on follow-up in three cases (TND), successfully substituted with sulfonylurea (SU) in three cases, and continued in four cases (PND). Molecular genetic testing is essential in cases with NDM for guiding mode of therapy as SU receptor defects can be successfully treated with oral SU instead of insulin injections. SU was more effective in achieving diabetes control in cases with KCNJ11 mutations.

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Acknowledgments

Mona Hafez, Mona Hassan, and Fatma El Mougy designed the work; Noha Musa collected the patients and the scientific data. Fatma El Mougy, Sahar Sharaf, and Sherif Mofeed did the biochemical tests; Michel Polak and Helene Cave carried out molecular diagnosis at their center in Paris; and Noha Musa did the follow-up of the patients’ treatment and control for a 1-year period. Noha Musa, Mona Hafez, Mona Hassan, Fatma El Mougy, and Sahar Sharaf shared in writing the paper.

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Authors and Affiliations

  1. Diabetes, Endocrine and Metabolism Pediatric Unit, Cairo University, Cairo, Egypt

    Noha Musa, Mona Hafez & Mona Hassan

  2. Department of Clinical and Chemical Pathology, Cairo University, Cairo, Egypt

    Fatma El-Mougy, Sahar Sharaf & Sherif Mofeed

  3. Hôpital Universitaire Necker Enfants Malades, INSERM U845, Paris, France

    Michael Polak

  4. Department of Genetics, Robert Debré Hospital, Paris, France

    Helene Cave

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  1. Noha Musa
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Correspondence to Noha Musa.

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Musa, N., Hafez, M., Hassan, M. et al. Clinical, molecular, and therapeutic aspects of NDM in ten cases with diabetes in 1st 6 months of life. Int J Diabetes Dev Ctries 36, 81–88 (2016). https://doi.org/10.1007/s13410-015-0431-z

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  • DOI: https://doi.org/10.1007/s13410-015-0431-z

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