Background: Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant inherited disease caused by heterozygous inactivating mutations in the glucokinase (GCK) gene. It mostly presents with mild fasting hyperglycaemia. MODY2 accounts for 2%5% of all diabetes cases. It is treated with diet only, and complications are extremely rare. We presented here a family with MODY2 caused by a novel heterozygous p.E51*(c.151.G>T) mutation of the GCK gene.
Case: A 17-year-old girl was admitted to our department because of fasting hyperglycaemia. Parents had no consanguinity. Father and grandfather were diagnosed with diabetes. On physical examination Body mass Index was 30.2 kg/m2 (>95 p) She had not acanthosis nigricans. Pubertal assessment revealed Tanner V. Serum autoantibodies against glutamic acid decarboxylase, islet cell antibodies, and anti-insulin autoantibodies were negative. Blood glucose level was repeatedly checked and showed fasting hyperglycaemia (132 mg/dl) as well as an elevated haemoglobin A1c level (6.6%; reference range, 4.8%5.9%). A standard oral glucose tolerance test with 75 g of glucose equivalent was performed with a fasting glucose of 130 mg/dl and a 2-h glucose of 159 mg/dl. The fasting insulin concentration was 6.9 μU/ml and 27 μU/ml after 2 h. Considering the clinical and family history, mutation analysis of the GCK gene was performed. Complete sequencing of coding exons and intron-exon boundaries of the GCK gene was carried out in the patient. Genetic analysis of case identified a heterozygous mutation (c.151.G>T) leading to stop codon (p.E51*) in GCK gene. Family members were screened for this mutation. The same mutation and mild hyperglycaemia were found in the patients father and the two-sisters but was absent in the mother.
Conclusion: GCK mutation screening should be considered in patients with mild early-onset hyperglycaemia, family history of impaired glycaemia, and negative ß-cell antibodies. In addition family members of patients with MODY should be screened.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology