Introduction: An activating mutations in the ABCC8 gene cause both transient and permanent neonatal diabetes mellitus (DM) or MODY 12. In relation to the variant in the ABCC8 gene, patients may also present with either neonatal hyperinsulinism and/or DM later in life. Besides, the same variant can cause different phenotypic features among family members. Response to the sulfonylurea treatment may vary between patients.
Aim: To present the clinical features and response to sulfonylurea treatment in an obese adolescent misdiagnosed with type 2 DM, who was later found to have a heterozygous variant in the ABCC8 gene.
Case: A 13-year-old girl was admitted to the endocrinology clinic because of hyperglycemia. At presentation, she had no polyuria, no polydipsia or weight loss. Her birth weight was 4500 g and no medical record of hyper or hypoglycemia in the neonatal period was present. Her father, mother and grandmother were diagnosed with DM and received insulin or oral antidiabetics. Her weight was at +3.43 SD, height at +1.22 SD, BMI was 30.3 kg/m2 (+2.63 SD); she had Tanner stage V puberty and acanthosis nigricans. Fasting blood glucose 332 mg/dL (N, 60-100), insulin 37.4 mIU/mL (N, 2.6-24.9), C-peptide 5.69 ng/mL (N, 0.9- 7.1), HbA1c 10.4% (N, 4-6), diabetes autoantibodies were negative and ketonuria or acidosis on blood gas analysis were absent. The patient was diagnosed with type 2 DM, thus metformin (2 x 1000 mg) and low dose insulin glargine (0.25 U/kg/day) were administered. Because of ongoing hyperglycemia and elevated HbA1c level at follow-up, insulin aspart was initiated. Due to the remarkable family history of DM in three generations, negative diabetes antibodies and continuing insulin requirement, MODY was considered. A next generation sequencing of MODY genes (GCK, HNF1A, HNF1B, HNF4A, KCNJ11, INS and ABCC8 genes) revealed a previously identified heterozygous variant c.1252 T> C in the ABCC8 gene. The mother was heterozygous for the same variant. A trial with sulfonylurea (gliclazide) was initiated and increased, while insulin aspart was discontinued. The patient is currently being treated with gliclazide (120 mg/) and insulin glargine (0.7 U/kg/d).
Conclusion: Molecular genetic analyses of MODY genes in patients with apparent type 2 DM, who have a strong family history of DM and on-going need for insulin treatment, may provide accurate diagnosis. In these cases, transition from insulin to sulfonylurea therapy may allow better glycemic control and improvement in the quality of life.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology