11-year-old female, admitted in the emergency room due to postprandial hyperglycemia (350 mg/dL) in her father´s glucometer without ketosis or acidosis. She referred one-month evolution of mild symptoms, as polydipsia, polyuria, sporadic abdominal pain and nocturia.
She was the first child of non-consanguineous parents, born full term at vaginal delivery with a birth weight of 3760g (90th percentile). Since 5-years-old her weight was between 85th-97th percentiles (classification: overweight). There was family history of diabetes. 43-year-old father was diagnosed with type 2 diabetes (T2D) since he was 10-years-old (detected in routine laboratory tests but without symptoms). Initially he was treated with oral antidiabetic drugs (metformin and glibenclamide). He started insulin therapy at 23-years-old due to persistent hyperglycemia with high glucose values (600 mg/dL) and symptoms like polydipsia and polyuria. He was never overweight and actually he has diabetic retinopathy. 73-year-old paternal grandmother was diagnosed with T2D at 50-years-old and she is currently under insulin therapy. The remaining family history is irrelevant.
Analytically: there was no ketosis (ketonemia 0.1); no acidosis in venous gasometry; normal complete blood count; normal values of albumin, magnesium, phosphate, potassium, sodium, chloro, and calcium; normal values of triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein; negative celiac disease screening; HbA1c 12.0%; normal thyroid function and negative antibodies; insulin 28.5 (reference value: 6-27 uUI/mL) and C-peptide 2.22 (reference value: 0.8-6.0 ng/mL).
Auto-immunity study was negative for glutamate decarboxylase autoantibodies, insulin autoantibodies, zinc transporter autoantibodies, islet of Langerhans autoantibodies and HLA DQ2-DQ8. A genetic study was requested on suspicion of Monogenic Diabetes (MODY): the variant c.602A>Cp (His201Pro) in the HNF4-alpha gene was found in heterozygosity. Subsequently, a genetic study was also performed on the father, and the same variant was found.
Currently, 9 months later, she is under metformin 500 mg twice a day, and multiple daily insulin injections therapy with requirements of 0.6 U/kg/day and HbA1c 8.1%.
The authors decided to present this case since this genetic variant is not described in the literature. The diagnosis of this adolescent also allowed the reclassification of the father´s diagnosis of diabetes. A correct classification of diabetes is important because it can predict the clinical course of the disease, clinical orientation and pharmacological treatment.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology