An autopsy is conducted on a stillborn female fetus exhibiting multiple lethal congenital malformations and osteosclerosis. Analysis of lipids accumulated in tissues showed high levels of desmosterol and extremely low levels of cholesterol. Given the skeletal malformations and the lipid profiles obtained from this fetus, the pathologist makes a diagnosis of desmosterolosis. Which of the following enzymes was most likely defective in this fetus resulting in the lethality?
A) 7-dehydrocholesterol reductase
B) 24-dehydrocholesterol reductase
C) HMG-CoA reductase
D) mevalonate kinase
E) squalene monooxygenase

Question

Quizplus · Accepted Answer

Desmosterolosis is caused by a defect in the enzyme 24-dehydrocholesterol reductase, which is responsible for converting desmosterol to cholesterol. This defect leads to the accumulation of desmosterol and low levels of cholesterol, resulting in the observed symptoms.  Desmosterolosis is an extremely rare disorder, but the presentations are useful for an understanding of the role of cholesterol in early neonatal developments. Skeletal abnormalities found in desmosterolosis are similar to, but more severe than, those presenting in SLOS. Desmosterolosis results from a defect in the gene encoding 3-β-hydroxysterol d-24-reductase (DHCR24), which catalyzes the reduction of the d-24 double bond of sterol intermediates during cholesterol biosynthesis. Loss of DHCR4, therefore, causes a loss of cholesterol production with accumulation of the intermediate, desmosterol.

An Autopsy Is Conducted on a Stillborn Female Fetus Exhibiting