Gaucher disease

Gaucher disease: features, diagnosis and treatment

Gaucher disease belongs to the group of sphingolipidoses - rare hereditary lipid storage diseases that arise due to a defect in the gene responsible for the synthesis of the lysosomal hydrolytic enzyme pglucocerebrosidase fglycosidase. Defect and deficiency of this enzyme lead to impaired utilization of lipids and their accumulation in macrophages, mainly of the bone marrow, spleen and liver.

There are three types of Gaucher disease. Type 1, or benign, is 30 times more common among Western European Ashkenazi Jews. There are no neurological disorders, and visceral changes are associated mainly with hematopoietic organs, enlarged spleen, hypersplenism and bone tissue destruction. With the other two types, no ethnic predominance was noted. Type 2 is a malignant form of the process with severe neurological disorders that manifest themselves in newborns and lead to death in the first 2 years of life. Type 3 is characterized by variability in visceral and neurological disorders and is less malignant in course than type 2. The variety of forms of Gaucher disease is due to the heterogeneity of mutations in the glycosidase gene.

Gaucher disease is inherited recessively, meaning that children of an affected parent usually do not get the disease. However, there are cases of illness among nephews, aunts and uncles. The gene mutation leading to Gaucher disease apparently contributed to the evolutionary selection of individuals with this defect, which determined the prevalence of this mutation in one of the ethnic groups.

The pathogenesis of Gaucher disease is associated with the accumulation of lipids - glucocerebrosides in macrophages. Due to their reproduction, the spleen and liver enlarge, and the structure of the tubular bones is disrupted. The clinical picture first manifests itself as an asymptomatic enlargement of the spleen, then the liver, as well as bone pain. Cytopenia gradually increases in the blood. An abundance of Gaucher cells is found in the bone marrow, liver and spleen.

The diagnosis of Gaucher disease can be suspected when specific Gaucher cells (a lymphocyte-like nucleus, eccentrically located, and a very wide light periphery) are detected in a bone marrow smear or splenic biopsy. Confirmation of the diagnosis occurs by determining the activity of glucocerebrosidase in blood leukocytes or skin fibroblasts. The discovery of two alleles with pathogenic mutations in the glycosidase gene confirms the hereditary nature of the disease.

Treatment of Gaucher disease is aimed at replacement therapy, which consists of regular administration of exogenous glycosidase into the patient's body. This makes it possible to reduce the accumulation of glucocerebrosides in tissues and slow down the progression of visceral and neurological disorders. A promising treatment method is gene therapy, which is aimed at restoring the normal functioning of the damaged gene. However, this technology is currently in the research and development stage. An important place in the treatment of Gaucher disease is occupied by palliative therapy, which is aimed at improving the patient’s quality of life and preventing complications.