A novel heterozygous mutation in the glucokinase gene conferring exercise-induced symptomatic hyperglycaemia responsive to sulfonylurea

Abstract

AimTo describe the atypical phenotype and genotype of an adolescent girl with symptomatic exercise-induced hyperglycaemia, responsive to sulfonylurea treatment. MethodsChart review, gene sequencing, and blinded continuous glucose monitoring (Medtronic iPro2) were used to characterise the case. ResultsA novel heterozygous mutation p.Q219x (c.655C>T) in exon 6 of the glucokinase gene (NM_000162.3) was confirmed in the patient and father. Initiation of gliclazide 20mg twice daily was associated with resolution of symptoms and normalization of haemoglobin A1C (5.6%). Blinded continuous glucose monitoring demonstrated significantly less time spent in the hyperglycaemic range (sensor glucose>8.0mmol/L) when on twice daily gliclazide versus intermittent or no gliclazide (mean minutes/day with sensor glucose>8mmol/L: 53.6±90.0 vs. 307.9±246.6; P=0.04). ConclusionsThis novel mutation in the glucokinase gene led to atypical symptomatic exercise-induced hyperglycaemia that was responsive to low dose sulfonylurea with self-reported additional benefit after reduction of carbohydrate intake. We postulate that her atypical clinical presentation was related to the intense elite-level physical activity combined with carbohydrate loading before exercise.