Question 177

Question:

A 3-year-old boy with mental retardation has hepatosplenomegaly. Analysis of tissue obtained on biopsy of the liver shows unusually large amounts of glucocerebroside. Which of the following enzymes is most likely to be deficient?

Correct Answer: C.  Lysosomal hydrolase

The clinical picture suggests a diagnosis of Gaucher’s disease. Gaucher’s disease is the most common variant of a group of diseases called lysosomal storage diseases which are caused by deficiency in any one of many lysosomal enzymes. Gaucher’s disease occurs due to the deficiency of beta-glucocerebrosidase, a lysosomal hydrolase (choice C) that converts glucocerebroside to cerebroside. Glucocerebroside accumulates and can then cause the clinical picture of mental retardation and hepatosplenomegaly.
Hormone-sensitive lipase (choice A) is an enzyme found in the cytosol of adipocytes that hydrolyzes triglycerides to free fatty acids and glycerols.
Lipoprotein lipase (choice B) is an enzyme found in endothelial cells lining capillaries that hydrolyzes triglycerides circulating in chylomicrons and VLDLs into free fatty acids and glycerols.
Sphingolipid synthase (choice D) is an enzyme that uses ceramide as a substrate for sphingomyelin production.
Tissue phospholipase (choice E) is an enzyme that hydrolyzes phospholipids into free fatty acids and other lipophilic products.