Successful Transfer from Insulin to Oral Sulphonylurea in an Infant and His Mother with Monogenic Diabetes Due to a Heterozygous Missense Mutation in the ABCC8 Gene

Neonatal diabetes mellitus (NDM) which can be transient or permanent is a rare form of monogenic diabetes which usually presents in the first 6 months of life. Mutations in the KATP channel genes (ABCC8 and KCNJ11) are the most common cause of NDM. NDM due to ABCC8 and KCNJ11 mutations can be sulphonylurea-responsive. Herein, we present the successful transfer from insulin therapy to sulphonylureas following the identification of an ABCC8 mutation in a patient with NDM and his affected mother who was on insulin therapy for 8 years.

Case:

A 7-month-old male presented with hyperglycemia. He was born at term by caesarean delivery to non-consanguineous parents after an uneventful gestation with a birth weight of 2750 gr. His mother and two aunts had diabetes and were on insulin therapy. On physical examination, his length was 66 cm (-1.56 SD) and weight was 8.4 kg (0.1 SD). Other physical findings were normal. In laboratory examination, blood glucose was 304 mg/dL, insulin: 1.9 µU/mL, C-peptide: 0.38 ng/mL, and hemoglobin A1c (HbA1c) was 8.4%. In urine analysis, he had (+++) glycosuria and mild ketonuria. He had no acidosis in blood gas analysis, and anti-glutamic acid decarboxylase antibodies were negative. Normoglycemia was achieved by insulin therapy. Molecular genetic analysis identified a heterozygous missense mutation, p.E208K (c.622G>A) in exon 5 of ABCC8 gene. The patient’s mother was heterozygous for the same mutation. A trial of sulphonylurea therapy in the patient and his mother has shown a satisfactory glycemic response. Insulin therapy was weaned successfully in both the patient and his mother. HbA1c level declined from 8.4% to 6.0% with sulphonylurea therapy. In conclusion, mutation analysis in patients with monogenic diabetes can provide fundamental changes in management of their diabetes and allows for genetic counseling in the family.