Аңдатпа
INTRODUCTION: The hereditary forms of rickets are a current issue in pediatric nephrology, endocrinology and genetics. This is due to the fact that different forms of rickets have clinical polymorphism which is probably based on the genetic heterogeneity. According to The portal for rare diseases and orphan drugs, the prevalence of vitamin D-dependent rickets type I (VDDR-I) is 1-5:10000 and the prevalence of vitamin D-dependent rickets type II (VDDR-II) in the population is unknown. It is known that the development of VDDR-I is associated with a deficiency of 1ɑ-hydroxylase in the kidney as a result of a defect in the CYP27B1 gene, which leads to impaired oxidation of calcidiol to calcitriol. In this report we aimed to present cases from our practice and demonstrate the clinical and genetic features of hereditary rickets. METHODS: Retrospective (medical records) and prospective (physical examination, laboratory diagnostics, genetic analysis). RESULTS: There were 3 sisters and 1 boy (from another family) with typical symptoms in our University Hospital. What is noted that the parents of the children are healthy, the relatives with such diseases had not been identified, and the prenatal history was unremarkable in both cases. According to the history of sisters, it is known that the disease manifestation was at the age of 1-1.5 years. The sisters had convulsive syndrome, spontaneous fractures, hyperesthesia and skeletal deformities. The girls were not able to go, lagged behind in physical development. There were the significant hypocalcemia and a very high level of alkaline phosphatase. Phosphate diabetes was excluded. The diagnosis of VDDR was made on the basis of clinical and laboratory data. The treatment included high doses of vitamin D3 (initially - 60000 IU / day, today - 10000 IU / day) with the control of calcium, alkaline phosphatase and 25 (OH) D3. On the background of therapy, clinical and laboratory improvement was noted. Nowadays girls are physically active, bone deformities are saved only in the eldest of sisters. Another patient, a boy, 2015 y.o., was admitted only in the spring of 2018, previously was observed by a neurologist. The clinical symptoms also had a lag in physical development, convulsions; he was not able to move by himself. There was no clinical improvement after the treatment of vitamin D3. Then they began therapy with the active form of vitamin D - calcitriol (Rocaltrol at a dose of 0.25-0.5 mg). As a result of the initiated therapy, there is an improvement in the psychophysical development, normalization of laboratory parameters. The result of genetic research proved our clinical diagnosis: a mutation was detected in the exon 8 of the CYP27B1 gene, which play the main pathogenic role in VDDR-I. CONCLUSIONS: These clinical observations demonstrate not only the genetic basis of the disease, but also the difficulty of verifying the diagnosis, the definition of a specific type of VDDR, and, consequently, the choice of management for patients. Such orphan diseases undoubtedly require a multidisciplinary approach with the participation of nephrologists, neurologists, and geneticists. Moreover, genetic verification of the diagnosis is also necessary for medical and genetic counseling in matters of further family planning.