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.