Which description matches homozygous dominant FH?

• A. -2 defective LDL genes; 100% defective LDL receptors; LDL levels over 600 mg/dL
• B. -1 defective LDL gene; 50% defective receptors; LDL 300-350 mg/dL
• C. -2 normal LDL genes; LDL <100 mg/dL
• D. -2 defective LDL genes; 50% defective receptors; LDL 600 mg/dL

Answer: (A)

Two defective LDL receptor genes produce no functional LDL receptors, so the liver can’t clear LDL from the bloodstream. This makes the LDL cholesterol soar, and when both copies are defective, the situation is especially severe, with LDL levels typically well over 600 mg/dL. This mirrors homozygous dominant familial hypercholesterolemia, where having two mutant alleles results in a maximal loss of receptor activity and very high cholesterol.

In contrast, having one defective gene leaves some receptor activity, usually yielding LDL around 300–350 mg/dL. Normal genes on both copies keep LDL well under 100 mg/dL. The scenario with two defective genes but only partial receptor impairment isn’t consistent with the expected full loss of function when both alleles carry the defective variant, so the description with complete receptor loss and extremely high LDL best matches the homozygous dominant form.