ESPE Abstracts

Introduction: HNF1A-MODY (MODY3) is a common subtype of the Maturity Onset Diabetes of the Young (MODY), a monogenic autosomal dominant disease presenting as a nonketotic diabetes with onset usually during adolescence, or early adulthood. HNF1A-MODY is less common among children as the hyperglycaemia usually manifests after 10th year of life.

Aim: We describe a young girl presented with hyperglycaemia and glysosuria.

Subjects and methods: An 8.5-year-old girl was referred to our Department by a District Hospital with abdominal pain, nausea, urine glucose (+++) and elevated serum blood glucose (BG) (288mg/dl-16 mmol/l), with the suspicion of a newly developing type 1 diabetes (T1D). She received intravenous N/S 0.9%. She was one of twins, born at 36 weeks gestation, birth weight 2310gr; unrelated parents. Her father, 51 years old, had been on treatment for arterial hypertension and presumed type 2 diabetes (T2D) diagnosed 10 years ago, her mother and twin brother were healthy. On admission she had mild abdominal pain. Growth was on the 50^th percentile, prepubertal; BG normal, pH 7.44, HCO3 22.4mmolL, BE -2.3 mmol/l, biochemical and hormonal screening normal. Urine testing showed glycosuria, no ketones; subsequently negative for both. An oral glucose tolerance test (OGTT) is shown below:

During her hospitalization pre-and post-prandial BG testing was within normal range. Renal ultrasound revealed a renal cortex cyst with a calcified wall on the right, distension of the renal pelvis on the left kidney. Anti-GAD, IA2, ICA antibodies were negative. She was discharged on home BG (BMstix) self-monitoring and follow-up in Clinic. She has been well since with normal pre-and post-prandial BG, last HBA1c 5.5% (4.8-6). Patients’ DNA were tested employing an NGS Targeted Gene Panel of 7 MODY genes. The variant identified was confirmed by Sanger Sequencing exon 2 of HNF1A gene in patient’s and her father’s DNA.

Results: Genetic testing revealed that our patient and her father were heterozygotes for the novel HNF1A, c.454A>C, p.T152P, variant, classified according to ACMG criteria as Likely Pathogenic.

Conclusions: HNF1A-MODY patients could easily be misclassified as T1D or T2D. Most patients will need pharmacological treatment as they show progressive deterioration in glycaemic control; they are extremely sensitive to sulfonylureas. Molecular genetic diagnosis of the MODY subtype is of outmost importance for clinical diagnosis, disease progression prognosis and family counselling.