Endocrine Abstracts

Background: Heterozygous loss of function glucokinase mutations causes MODY with fasting hyperglycaemia (>5.5 mmol/l). We report a 2 year girl with a glucokinase mutation who presented unusually with stress induced hyperglycaemia and normal fasting blood glucose levels.

Case report: She presented with wheeze and was started on Salbutamol. Her blood glucose rose to 16 mmol/l with ketonuria. The hyperglycaemia was disproportionate to the severity of the illness. Hyperglycaemia settled after medication was stopped and she had fasting blood glucose levels below 4 mmol/l. Two weeks later she had an OGTT. Fasting glucose was 3.3 mmol/l and blood glucose at 2 h was 8 mmol/l.

When the results of the OGTT were discussed with mother she disclosed a family history of diabetes. Mother’s uncle was diagnosed with type 2 diabetes, started on Metformin and was then well controlled with diet alone. Genetic analysis revealed a heterozygous GCK splicing mutation (c.483+2_483+16del15). His daughter and grandson had fasting hyperglycaemia and tested positive for the same mutation.

We tested our patient for this mutation in view of the impaired glucose tolerance and family history. She tested positive for the same GCK splicing mutation. Interestingly she did not have fasting hyperglycaemia which is unusual for MODY with glucokinase mutation. It further emerged that the child’s mother had gestational diabetes and is awaiting genetic testing.

Conclusion: The molecular diagnosis of MODY is important to classify the diabetes, predict prognosis and screen asymptomatic family members. In this family four members carried the identical mutation but presented with varying phenotypes. We concur with the policy of central genetic testing for these patients.