ESPE Abstracts (2023) 97 P1-245

ESPE2023 Poster Category 1 Diabetes and Insulin (55 abstracts)

Combination of mutations in the HNF1A and ABCC8 genes: clinical polymorphism in members of the same family.

Irina Eremina , Elizaveta Raykina , Elena Titovich , Valentina Peterkova & Dmitry Laptev

Institute of Pediatric Endocrinology, Moscow, Russian Federation

Mutations in HNF1A gene underlie the development of maturity onset diabetes of the young type 3 (MODY3). Mutations in ABCC8 gene are the cause of neonatal DM and the rare MODY12, which is clinically similar to MODY3. In these forms of MODY, there is a high sensitivity to sulfonylurea. Patient A, 17 y.o. He was born to woman with gestational DM. At the age of 12.5, fasting hyperglycemia of 13 mmol/l was detected. Insulin therapy was not prescribed due to the parent’s refusal. At the 14.5 y.o, since his mother was diagnosed with MODY3, a pathogenic variant p.R54X in HNF1A was detected, a MODY3 was diagnosed. At the age of 15, he was hospitalized with hyperglycemia 13.8 mmol/l. HbA1c - 9.8%. Long-acting insulin was assigned. Subsequently, the patient used insulin irregularly and consumed large amounts of carbohydrates. His maximum HbAc1 was 20,5%. At 17 y.o, he was admitted to hospital: glycemia was 18.6 mmol/l, HbAc1 - 12.6%, islet antibodies were negative. Intensified insulin therapy (0.9 units/kg/day) led to the normalization of glycemia. Specific diabetic complications were not detected. In addition to the variant in the HNF1A, a p.R521X variant was found in the ABCC8. After 3 months, the boy was successfully transferred to glibenclamide 7.5 mg/day. Patient L, 37 y.o, proband's mother. At the age of 20, gestational DM was diagnosed: fasting glycemia was 6-9 mmol/l, she refused insulin therapy. At the 32 y.o, an examination for cholelithiasis revealed hyperglycemia, the variant p.R54 X in the HNF1A was detected. To date, she has not received hypoglycemic therapy, followed a carbohydrate-restricted diet. At the last examination at the age of 37, HbAc1 was 6.7%, a variant of p.R521X was found in the ABCC8 as in the son. Patient S, 8 y.o, proband's sister. HbAc1 – 5.4%, fasting glycemia – 4.7 mmol/l. There are variants of p.R54X in the HNF1A and p.R521X in the ABCC8.

Conclusion: MODY associated with variants in the HNF1A and ABCC8 is characterized by a different degree of carbohydrate metabolism disorders, depending on the location of mutation in gene and its severity. We have presented a description of clinical polymorphism in members of family with a combination of identical mutations in the two MODY genes. The more severe disease in proband, apparently, is due to the low compliance. Normoglycemia in sister may be due to age, which requires further dynamic observation.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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