Endocrine Abstracts

Introduction: Neonatal diabetes mellitus is a rare condition with an estimated incidence of 1 in 400 000 live births in the UK population. Half of these cases will have permanent neonatal diabetes mellitus (PNDM). We report a homozygous missense mutation (R397L) in the glucokinase (GCK) gene which is associated with PNDM, in an infant from a consanguineous Asian family.

Case report: The baby was born with a birth weight of 1.68 kg at 38 weeks gestation and presented with severe hyperglycaemia without ketosis from day 2 of life. Mother was diagnosed with gestational diabetes in her second pregnancy and has been on metformin since but she was treated with insulin during this (her 4th) pregnancy. The baby initially required an intravenous insulin sliding scale (insulin requirement 1 unit/kg per day) and at 4 weeks of age commenced on a continuous subcutaneous insulin infusion (CSII). The basal insulin rate was started at 0.025 units/h and was gradually increased up to 0.1 units/h (total daily dose 1 unit/kg per day). Bolus insulin doses of 0.1 units were given for 100 ml feeds with additional correction doses of insulin between 0.1 to 0.2 units depending on her pre feed blood glucose concentration. The insertion of subcutaneous cannula for insulin pump was a challenge due to her age and the lack of subcutaneous tissue. Stool elastase was normal excluding pancreatic agenesis. Gene sequencing identified a homozygous mutation, R397L, in the GCK gene which confirmed a diagnosis of PNDM.

Conclusion: The management of neonatal diabetes in challenging not least because of the associated IUGR. Although CSII therapy is likely to provide the best glucose control it is technically difficult. To date, five reported cases of PNDM have been shown to be due to homozygous or compound heterozygous inactivating mutations in the glucokinase (GCK) gene. In the heterozygous form, GCK mutations cause maturity-onset diabetes of the young (GCK-MODY). We concur with the policy of central genetic testing for these patients and suggest that CSII is the therapeutic intervention of choice.