Early identification of monogenic diabetes: implications on medical treatment and genetic counselling for an adolescent girl with MODY3

Result A 14 years old girl, who previously had been well, was incidentally found to have hyperglycemia by her diabetic mother. Her body mass index was 19 kg/m. General examination was unremarkable without any acanthosis nigricans. Fasting blood glucose was 6.4mmol/L and 2 hour glucose in oral glucose tolerance test was 15.3mmol/L. HbA1c was 7.5%. Fasting C-peptide was 3.2 μg/L (reference 0.9-7.1μg/L). Family history revealed that her mother developed diabetes at the age of 20 and had been managed as type 1 diabetes with insulin. Mother had satisfactory glycemic control despite the dosage of insulin remained relatively low for decade. However, she then got poor compliance to insulin injection after the age of 40, resulted in worsening of HbA1c to 11-12%. Furthermore, two maternal aunts were thought to have diabetes, but no further detail was available. A diagnosis of MODY was considered for the girl and molecular analysis confirmed MODY3 with heterozygous HNF-1a NM 000545.5: c.775G>T (p.Val259Phe) mutation. The patient was initiated on the treatment with low dose gliclazide. She could achieve good glycemic control without problem of significant hypoglycemia. Her most recent HbA1c was 5.7%. Gene sequencing confirmed that her mother also harbored the same mutation. After genetic counselling, insulin therapy of patient ’s mother was gradually switched to glimepiride by adult endocrinologist. Her HbA1c showed significant improvement from 12.2% to 7.1%. In addition, no mutation was detected for patient’s elder sister, indicated that she only had the population risk of developing diabetes.