Cholesteryl ester storage disease (CESD, OMIM #278000) and Wolman disease (OMIM 
#278000) are autosomal recessive lysosomal storage disorders caused by a 
deficient activity of lysosomal acid lipase (cholesteryl ester hydrolase, LAL). 
Human lysosomal acid lipase is essential for the metabolism of cholesteryl 
esters and triglycerides. In Wolman disease, LAL activity is usually absent, 
whereas CESD usually presents some residual LAL activity. In infants, poor 
weight gain, massive hepatosplenomegaly, calcified adrenal glands (present about 
2/3 of the time), vomiting, diarrhea and failure to thrive are indicative of 
Wolman disease. The clinical picture is more variable in CESD. Hepatomegaly 
and/or elevation of liver transaminases are almost always present. Hepatic 
steatosis often leads to fibrosis and cirrhosis. Other signs often include 
splenomegaly, high total cholesterol and LDL-cholesterol, elevated 
triglycerides, and low HDL-cholesterol. The diagnosis of LAL deficiency requires 
clinical experience and specialized laboratory tests. The diagnosis is based on 
finding deficient activity of acid lipase and/or molecular tests. Pilot 
screening projects using dried blood spot testing in 1) children with atypical 
fatty liver disease in the absence of overweight, 2) patients with dyslipidaemia 
and presence of hepatomegaly and/or elevated transaminases, 3) newborns/neonates 
with hepatomegaly and abdominal distension/failure to thrive/elevated 
transaminases are currently underway. Early diagnosis is particularly important 
for the enzyme replacement therapy. Human trials with recombinant LAL are 
currently ongoing, raising the prospect for specific correction of LAL 
deficiency in this progressive and often debilitating disorder.