A family case of Shwachman-Diamond syndrome in children with a rare genetic variant of the SBDS gene с.653G>A (p.Arg218Gln)

Shwachman – Diamond syndrome is a hereditary ribosomopathy which is manifested by exocrine pancreatic insufficiency, hematological disorders, stunted growth and bone deformities. The pathology is caused by mutations in the SBDS gene. Early detection of the disease and timely treatment, including the use of enzyme preparations, specialized nutrition and granulocytic colony-stimulating factors, contribute to improving the patients' quality of life and prognosis. A clinical case of a family manifestation of this syndrome is presented in the article. The diagnosis was made and confirmed by a genetic study only at the age of 1. From birth, the girl had clinical manifestations of atopic dermatitis, with a torpid course to therapy, characteristic stools, changes in the general blood test (GBT) in the form of leukopenia and neutropenia of varying severity, changes in the biochemical blood test (BCBT) in the form of increased liver enzymes. Also, the patient has an 8-year-old elder sister with similar changes in the GBT. To exclude the presence of pathogenic genetic variants of the SBDS gene in the cis-position, the girl's parents were examined. A pathogenic variant of the SBDS gene C.258+2TC in a heterozygous state was revealed in the girl's mother, while the father had the variant C.653GA (p.Arg218Gln) in a heterozygous state. Taking into account the hereditary nature of the disease, the girl's elder sister underwent a genetic examination as well at the age of seven. The study also revealed two pathogenic variants of the SBDS gene C.653GA (p.Arg218Gln) and C.258+2TC in a compound heterozygous state. Thus, SDS in the child was confirmed by genetic methods of examination. The case described in the article is aimed at attraction the pediatricians' attention to the correct assessment of GBT indicators (knowledge of age-related norms of the blood cells count and age-specific features of the leukoformula), the ability to count the absolute number of granulocytes. To clarify the nature of neutropenia (congenital, acquired), it is necessary to evaluate the GBT results in dynamics.