Clinical Information

Deficiency of lysosomal acid lipase (LAL) results in 2 clinically distinct phenotypes, Wolman disease (WD) and cholesteryl ester storage disease (CESD). Both phenotypes follow an autosomal recessive inheritance pattern and are caused by mutation in the LIPA gene.

WD, the early onset phenotype of LAL deficiency, is a lipid storage disorder characterized by vomiting, diarrhea, failure to thrive, abdominal distension, and hepatosplenomegaly. Peripheral blood lymphocytes are vacuolated and foam cells are present in the bone marrow. Approximately 50% of infants have adrenal calcifications. WD typically presents in the first weeks of life and is fatal in infancy.

CESD, the late onset phenotype of LAL deficiency, is clinically variable with patients presenting at any age with progressive hepatomegaly and often splenomegaly, leading to microvesicular steatosis and often liver failure. CESD is likely underdiagnosed and frequently diagnosed incidentally after liver pathology reveals findings similar to nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Birefringent cholesteryl ester crystals in hepatocytes or Kupffer cells in fresh-frozen tissues are visualized under polarized light and pathognomonic. Elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides lead to premature atherosclerosis.

Treatment options for WD and CESD have been limited but enzyme replacement therapy trials are now ongoing.