title: A novel heterozygous mutation in the glucokinase gene conferring exercise-induced symptomatic hyperglycaemia responsive to sulfonylurea.
abstract: OBJECTIVE
  To describe the atypical phenotype and genotype of an adolescent girl with symptomatic exercise-induced hyperglycaemia, responsive to sulfonylurea treatment.
  
  
  METHODS
  Chart review, gene sequencing, and blinded continuous glucose monitoring (Medtronic iPro2) were used to characterise the case.
  
  
  RESULTS
  A 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>8.0 mmol/L) when on twice daily gliclazide versus intermittent or no gliclazide (mean minutes/day with sensor glucose > 8 mmol/L: 53.6 ± 90.0 vs. 307.9 ± 246.6; P=0.04).
  
  
  CONCLUSIONS
  This 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.
authors: Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, K1H 8L1, Canada; Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, Children's Hospital Cairo University, Cairo University, 11562 Cairo, Egypt.
authors: M S E
authors: MS
authors: Ebrahim
authors: Division of Endocrinology and Metabolism, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, K1H 8L1, Canada. Electronic address: lawson@cheo.on.ca.
authors: M L
authors: ML
authors: Lawson
authors: Metabolics, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, K1H 8L1, Canada.
authors: M T
authors: MT
authors: Geraghty
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000502:physiology; D015444:Exercise; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D009154:Mutation; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D013453:Sulfonylurea Compounds; D005941:Glucokinase
keywords: Exercise; Glucokinase; Heterozygote; MODY2; Sulfonylurea compounds