Modern concepts about lysosomal acid lipase deficiency (review)

Lysosomal acid lipase deficiency is a rare heterogeneous autosomal recessive heterogeneous genetic disorder whose manifestations often result in severe morbidity and mortality. The development of the disease is associated with the accumulation of cholesterol esters and triglycerides in organs and tissues, which in turn leads to the development of atherosclerosis, hepatosplenomegaly, liver cirrhosis, malabsorption syndrome and other symptoms. The true prevalence of the disease is unknown, the estimated incidence in Russia is 1 : 100,000–150,000 of the child population. Depending on the residual activity of the enzyme, 2 variants of the clinical course of the disease are distinguished. The most severe and also rare variant is Wolman’s disease, identified and described in 1961 by Israeli neurologist Moshe Wolman. This disease progresses during the first year of a child’s life and in most cases, due to the difficulties of diagnosis, leads to the death of patients. A milder but more common variant of LAL-D, occurring in children over one year of age and adults, is cholesteryl ester storage disease, described in 1968. The nonspecificity of symptoms of LAL-D at an early stage leads to the fact that the diagnosis of this condition is prolonged or missed by clinicians. An increase in liver enzymes in combination with hepato- and splenomegaly, dyslipidemia should alert the doctor and lead to early diagnosis of LAL-D even at the outpatient stage of examination, thereby increasing the duration and quality of life of patients. Differential diagnosis is carried out with Gaucher disease, Niemann–Pick disease, familial hypercholesterolemia, non-alcoholic steatohepatitis and other storage diseases. The main method of treatment is enzyme replacement therapy with sebelipase-alpha. Studies have shown its effectiveness in increasing the life expectancy of patients. It is recommended to use a multidisciplinary approach in the management of patients with LAL-D at all stages, since the disease is characterized by damage to many organs and systems and requires complex therapy. The biochemical and pathophysiological processes occurring in the body with deficiency of lysosomal acid lipase are considered.