Familial Hypercholesterolemia Management Flashcards

Which genetic mutation accounts for the majority of familial hypercholesterolemia cases in most populations?

Answer: LDLR loss-of-function mutation

LDLR loss-of-function mutations are responsible for approximately 85-90% of molecularly confirmed FH cases.

A child of two parents with heterozygous FH has what probability of inheriting homozygous FH?

Answer: 25%

With both parents carrying one FH allele, Mendelian inheritance gives a 25% chance of inheriting both defective alleles.

The Dutch Lipid Clinic Network (DLCN) score uses which combination of criteria to diagnose FH?

Answer: Family history, clinical signs, LDL-C level, and genetic testing

The DLCN score incorporates family history, clinical signs (xanthomas, corneal arcus), LDL-C levels, and DNA analysis into a weighted scoring system.

Which LDL-C threshold in an adult without other risk factors most strongly suggests homozygous FH rather than heterozygous FH?

Answer: LDL-C >400 mg/dL

Untreated LDL-C levels exceeding 400 mg/dL (often 500-1000 mg/dL) are characteristic of homozygous FH, whereas heterozygous FH typically presents with LDL-C of 190-400 mg/dL.

Tendon xanthomas in FH patients are most commonly found at which anatomical site?

Answer: Achilles tendon

Achilles tendon xanthomas are the classic and most common tendinous xanthoma location in FH, detectable by ultrasound even when not palpable.

Cascade screening for FH is most efficiently initiated using which approach?

Answer: Reverse cascade from the index case to first-, second-, and third-degree relatives

Reverse cascade screening from the index case outward to biological relatives is the most cost-effective strategy for identifying FH in families.

For a child with suspected homozygous FH, at what age should LDL apheresis typically be initiated if LDL-C remains severely elevated despite maximal medical therapy?

Answer: By age 10-12

Guidelines recommend initiating LDL apheresis by age 10-12 in HoFH patients with inadequate response to pharmacotherapy to prevent early cardiovascular events.