Ridotta attività della lipasi acida lisosomiale: un possibile ruolo patogenetico nella nafld?

Lysosomal Acid Lipase (LAL) is a hydrolase that plays a key role in intra-cellular cholesterol trafficking. A reduced LAL activity promotes an increased lysosomal cholesterol esters storage, as observed in two recessive autosomal genetic diseases. Wolman disease is characterized by total LAL deficiency and has an early onset phenotype with rapid multi-organ failure. Cholesterol ester storage disease (CESD) may develop during childhood and adulthood and has a less severe phenotype characterized by accelerated atherosclerosis, dyslipidemia and fatty liver rapidly progressing to fibrosis and cirrhosis. The natural history of LAL deficiency in adults is not well defined and the diagnosis is often incidental. LAL deficiency has been suggested as a possible unrecognized cause of dyslipidemia and fatty liver. Therefore, non-obese patients with unexplained persistent elevation of serum liver enzymes and LDL cholesterol should be tested for LAL deficiency. Recently, a reduced LAL activity was reported in adult subjects with non-alcoholic fatty liver disease (NAFLD) suggesting a possible role of LAL in the pathogenesis and progression of the disease. However, whether low LAL activity contributes to liver damage progression, or is itself a consequence of liver failure is still unknown. A better knowledge of the role of LAL may provide new insights in the pathogenesis and progression of NAFLD.