Abstract
Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive lysosomal storage disease caused by deleterious mutations in the LIPA gene. Occurrence is worldwide estimated to be 1 : 130 000 to 1 : 300 000 live births.
Patients pre- senting in infancy have the most rapidly progressive disease, developing signs and symptoms in the first weeks of life and rarely surviving beyond 6 months of age (Wolman disease). Children and adults typically present with some combination of dyslipidemia, hepatomegaly, elevated transaminases, and microvesicular hepatosteatosis on biopsy - cholesteryl ester storage disease (CESD).
Liver damage with progression to fibrosis, cirrhosis and liver failure occurs in a large proportion of patients. Elevated low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels are common features, and cardiovascular disease may manifest as early as childhood.
The lipid profile is very similar as we can see in familial hypercholesterolemia, so it is not surprising that LAL-D is under-recognized in clinical practice. This article provides practical guidance to lipidologists, on how to recognize individuals with this disease and, current management options are reviewed in light of the development of enzyme replacement therapy with sebelipase alfa, a recombinant human lysosomal acid lipase enzyme and is an update of a 2019 article with the addition of more detailed information on genetic testing options.