ESPE Abstracts

Сlinical case: Patient M., born at 35 weeks, the first of monochorionic twins with weight 3890 g (SDS 2.85), length 53 cm (SDS 2.71). From the first hours of life, the patient experienced hypoglycemia up to 1.9 mmol/l, which was relieved by intravenous glucose with a high utilization rate of up to 15 mg/kg/min. CHI was diagnosed at the age of 1 month (glycemia 2.1 mmol/l, insulin-15.2 µIU/ml). Diazoxide therapy was prescribed - 7.3 mg/kg/day. From the age of 3 months, the patient experienced more frequent episodes of hypoglycemia; the dose of diazoxide was increased to 17 mg/kg/day. Failed to get compensation, octreotide was added to therapy at a dose of 5 mcg/kg/day. Subsequently, the patient was transferred to injections of long-acting Lanreotide at a dose of 60 mg. Currently, the dose of Diazoxide is 17.8 mg/kg/day, the dose of Lanreotide is 90 mg once every 28 days. According to a molecular genetic study (NGS sequencing), a previously described pathogenic mutation in the GCK gene was identified: c.641A>G, p.Tyr214Cys. The monozygotic twin, without clinical signs of CHI, also underwent NGS- the same mutation was detected, but the alternative allele was only 13%. The patient's parents were examined and no mutations were identified. Based on the results of the examination, the twins were diagnosed with a somatic variant in the GCK gene, with different percentages of carriage of the mutant allele. At 6 months the patient was diagnosed with primary hypothyroidism with goiter (TSH 25.34 mIU/l, T4-8.0 pmol/l); therapy with Levothyroxine sodium was initiated. The mother was also diagnosed with primary hypothyroidism. The patient underwent whole exome sequencing; no mutations explaining the familial form of primary hypothyroidism have been identified

Conclusion: Considering the presence of a healthy monozygotic twin, with the presence of an alternative alley of 13% and the absence of mutations in the parents, we assume the presence of a somatic mutation in the patient. The presence of primary hypothyroidism in the patient and his mother is probably a consequence of a monogenic disease that could not be identified.