Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes with autosomal dominant inheritance and usually develops before 25 years. Heterozygous inactivating hepatocyte nuclear factor 4A (HNF4A) mutation is a rare subtype of MODY.
A 14-year-old girl was admitted to our clinic due to fatigue and polyuria, and hyperglycemia was detected afterward. She was born full term with birth weight of 5500 g (4.9 SD score) and had no postnatal hypoglycemia. Her parents were not relatives and family history revealed no diabetes. Physical examination revealed a height of 163 cm (SD score 0.29), weight 64.7 kg (SD score 1.2), and body mass index of 24 kg/m2 (SD score 1.2). Neither acanthosis nigricans nor striae were found. Laboratory analyses showed C-peptide 1.66 ng/mL (normal, 0.9-7.1 ng/mL), glycated hemoglobin (HbA1c) 8.8%, normal lipid profile, and negative autoantibodies regarding diabetes. Urine analysis showed 2+ glycosuria and no ketosis. We started only insulin glargine (0.2 unit/kg/day) with most probable diagnosis of MODY. Normal glycemia was improved and no hypoglycemia was seen with this treatment. HbA1c was decreased to 6.3%.
Genetic analysis revealed a de novo p.C93Y (c.278G>A) heterozygous novel change in the HNF4A. Insulin treatment was stopped and low-dose sulfonylurea (5.0 mg/day) initiated when the diagnosis of MODY 1 was proved. After five months of the treatment onset, fasting glucose was 111 mg/dL, insulin 11 IU/mL, C-peptide 2.2 ng/mL, and HbA1c was 5.8%.
Genetic testing should be considered to establish an accurate diagnosis and provide an opinion to determine the appropriate type of treatment.