Il trattamento dei difetti genetici ed acquisti di lipasi acida lisosomiale = The treatment of primary and secondary lysosomal acid lipase deficiency

Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesteryl esters and triglycerides, that reach the lysosomal compartment through the endocytosis of lipoproteins, or from the cytosol through the autophagic process. When LAL activity is lacking, cholesteryl esters and triglycerides accumulate in the body, causing severe pathologic manifestations, especially in the liver, spleen and hematopoietic cells, in the presence of atherogenic dyslipidemia. Two forms of genetic LAL deficiency (LAL-D) have been described: Wolman disease, the severe and fulminant type, and cholesteryl ester storage disease, a milder and late form. In addition, acquired LAL-D has been described in some pathologic conditions, as NAFLD and other advanced hepatopathies. To date, a guideline for the management of genetic LAL-D is not available, but early diagnosis and treatment is essential. Pharmacological management has been recently transformed by the availability of a recombinant human LAL for enzyme replacement therapy, which has been shown effective and safe in patients with genetic LAL-D. In addition, monitoring and management of associated complications is indicated. Regarding acquired LAL-D, dedicated studies are needed to clarify the relationship between LAL-D and NAFLD and, in particular, the possible prognostic role of LAL activity in NAFLD progression.