Wolman disease

Wolman disease (WD), an autosomal recessive disorder, is caused by very low or absent lysosomal acid lipase (LAL) activity, resulting in organ accumulation of cholesteryl esters and triglycerides. Patients with WD present during infancy with steatorrhea, chronic emesis, failure to thrive, and hepatosplenomegaly. Without treatment, patients usually die during the first year of life. A moderate phenotype of LAL deficiency, known as cholesteryl ester storage disorder (CESD), correlates with higher residual LAL activity than WD. Patients with CESD present later in life with hepatomegaly, hyperlipoproteinemia, and premature atherosclerosis. Both WD and CESD are diagnosed by enzymatic assay of LAL and confirmed by genetic testing. Several treatments are available. Enzyme replacement therapy (ERT) is under study and may prove effective in both WD and CESD. Lipid-lowering drugs and a low-fat diet help manage dyslipidemia in CESD. Liver transplantation may be performed for hepatic failure or cirrhosis in CESD. Bone marrow transplantation has been carried out for WD. Current efforts include determining the long-term effects of ERT, reduce transplantation-associated complications, investigate more effective lipid-lowering drugs, or evaluate combinations of these therapies.