ESPE Abstracts (2021) 94 P2-158

ESPE2021 ePoster Category 2 Diabetes and insulin (72 abstracts)

A novel variant HNF1A gene (HNF1A-MODY) in a patient presenting with hyperglycaemia and glycosuria

Vasiliki Bisbinas 1 , Amalia Sertedaki 2 , Andreas Giannopoulos 3 & Zacharoula Karabouta 3

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1University of Bristol, Bristol, United Kingdom; 2Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, Νational and Kapodistrian University of Athens, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece; 32nd Paediatric Department, University General Hospital AHEPA, Thessaloniki, Greece


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 50th 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.

Time (mins)60΄120΄
BG(mg/dl) (mmol/l)76 (4.2)191 (10.6)230 (12.7)
Insulin (μIU/ml)5.62134.4
C-peptide(ng/ml)1.424.475.74
HBA1c (%)6

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.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

Online,
22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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