ESPE Abstracts

Background: MODY HNF1B variants are most frequently associated with extra-pancreatic manifestations like renal cysts [leading to renal cysts and diabetes (RCAD) syndrome], abnormalities of the uro-genital tract and hypomagnesemia, but may also cause MODY or renal structural disease in isolation, therefore cases of HNF1B MODY still remained largely undiagnosed. In Ukraine, there are currently three patients with MODY HNF1B de novo whole gene deletion.

Clinical case: A 17 year old male, was admitted to the nephrology department for a routine examination. According to the anamnesis, he has been observed by a nephrologist since the age of 7 with chronic pyelonephritis and congenital anomaly in the development of the kidneys (doubling of the right kidney). In the nephrology department the routine examination revealed hyperglycemia (10.5 mmol/l), there were no ketones in the urine. Due to hyperglycemia, the patient was transferred to the endocrinology department. The results of a general examination: height 176 cm (+0.1 SD), weight 58 kg, BMI 18.7 kg/m² (15 p.c.), Heart rate – 80/min, BP - 125/80 mm (75-90 p.c.). He had normal male external genitalia, Tanner 4. The blood glucose level was 15.7 mmol/l, he also had glycosuria without ketonuria. There are no cases of diabetes in the family; however, the father suffers from chronic pyelonephritis. The results of an additional examination revealed high HbA1c (13.5%/, low C-peptide 0.25 ng/ml (0.7-1.9). Insulin was administered at a dose 0.6 U/kg. The ultrasound examination of abdomen confirmed a doubling of the right kidney, as well as a neoplasm in the liver (hemangioma?). Subsequent CT scan excluded a liver pathology. To continue the diagnostic search, the patient was tested for specific antibodies (GAD, IA2, ZnT8), the results of which were negative. Hereafter genetic testing using tNGS MODY panel was done, where it was found heterozygous pathogenic HNF1B whole gene deletion variant (NM_000458.4: c. (?_1)_(*4_?)del, p.(0?). The HNF1B whole gene deletion variant was also not detected in parents, and this result suggests that the variant has arisen de novo. Follow up management is needed to control BP and lab tests (liver function tests, magnesium, uric acid, renal function (eGFR, urea and creatinine), fecal elastase, PTH, urinary albumin), ultrasound of abdomen, CT of abdomen. Early treatment with ACE inhibitors should be also considered.