ESPE Abstracts (2019) 92 P3-318

Novel Mutation in HNF4-Alpha Gene and Reclassification of Diabetes in a Family

Maria Miguel Gomes1,2, Manuel C. Lemos3, Olinda Marques4, Sofia Martins1, Ana Antunes1


1Pediatrics Department, Braga Hospital, Braga, Portugal. 2School of Medicine, University of Minho, Braga, Portugal. 3Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. 4Endocrinology Department, Braga Hospital, Braga, Portugal


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.

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