[Lysosomal acid lipase deficiency (LAL-D) : Diagnostic and therapeutic options in an underdiagnosed disease]

Lysosomal acid lipase deficiency is an autosomal recessive storage disease caused by mutations in the LIPA gene. The accumulation of cholesteryl esters and triglycerides in hepatocytes lead to hepatomegaly with progressive fibrosis and liver cirrhosis. Characteristically, patients have a hepatomegaly combined with high serum levels of cholesterol, LDL-cholesterol and in some cases triglyceride, whereas HDL-cholesterol is decreased. Histologically, hepatocytes show a microvesicular steatosis with typically ballooned Kupffer cells. Even though histological morphology is typical, it is not characteristic. Therefore LAL-D is supposed to be an underdiagnosed disease with a high number of unreported cases misdiagnosed as uncharacteristic fatty liver disease (NASH, NAFLD, cryptogenic liver cirrhosis). Further, there is overlap with other storage diseases, complicating a correct diagnosis.

Until recently, different therapeutic options could not prevent development of liver cirrhosis. Patients with Wolman's disease have an especially rapid progression and die within the first six months of life. With the recent development of a new enzyme replacement therapy with sebelipase alfa (Kanuma ®), new therapeutic options with significant improvement of dyslipidemia and reduction of transaminases have become reality. Positive clinical results seem to have the potential to significantly raise life expectancy.

These new therapeutic options warrant an increase in awareness of LAL-D by clinicians and pathologists. Correct diagnosis of LAL-D is important for effective therapy and long-term survival.