A clinical case of pregnancy of a patient with a combination of two orphan diseases: familial partial lipodystrophy type 4 and HNF1A-MODY on the background of therapy with recombinant human methionyl leptin

Lipodystrophies are a group of orphan diseases (according to different sources, the prevalence of the disease varies from 1 to 5 cases per 1,000,000 population), which can be either hereditary or acquired. Diseases of this group represent a symptom complex characterized by varying degrees of loss of adipose tissue: complete (generalized lipodystrophy) or partial (partial lipodystrophy), as well as abnormal distribution of subcutaneous fat, provided that there is no influence of alimentary factors and catabolic conditions. Lipodystrophies are characterized by metabolic changes: dyslipidemia, carbohydrate metabolism disorders, insulin resistance, metabolically associated fatty liver disease. Separately, it is worth mentioning reproductive disorders, such as polycystic ovary syndrome, infertility, miscarriage, and others. A decrease in the body’s fat content leads to a decrease in the production of the hormone leptin, which affects the hypothalamic neurons that regulate hunger and satiety, and increases energy expenditure by stimulating thermogenesis. Hypoleptinemia is the main cause of metabolic disorders associated with lipodystrophy. Currently, a recombinant analogue of human leptin has been registered — metreleptin (methionyl leptin), which improves the quality of life of patients by achieving compensation for metabolic disorders, reducing hyperphagia, and also having a beneficial effect on fertility.HNF1A-MODY is diabetes mellitus with an autosomal dominant type of inheritance associated with heterozygous variants of the HNF1A gene, which is involved in the differentiation and functioning of the pancreas. The disease is characterized by onset at a young age, prevalence of postprandial hyperglycemia, presence of glucosuria, progressive course with a high risk of developing micro- and macrovascular complications, effectiveness of therapy with sulfonylurea drugs with the emergence of the need for insulin therapy over time.This article presents the first clinical case in Russia demonstrating the pregnancy of a patient with a combination of two orphan diseases: familial partial lipodystrophy type 4 and MODY 3 (list of rare (orphan) diseases of the Ministry of Health of Russia, dated February 6, 2023), who received pathogenetic treatment with metreleptin before confirmation of the fact of pregnancy.