WBR0096

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Cardiology
Prompt	[[Prompt::A 20-year-old man presents to the emergency department (ED) with an acute severe substernal chest pain. In the ED, his ECG shows ST-segment elevation in leads V1-V4. The patient denies recent physical trauma or illicit drug use. He has an otherwise unremarkable past medical history. Laboratory values show elevated troponin, LDL of 840 mg/dL, and HDL of 30 mg/dL. Which of the following is most likely true of this patient’s condition?]]
Answer A	AnswerA::The disease follows autosomal recessive inheritance
Answer A Explanation	[[AnswerAExp::Familial hypercholesterolemia is caused by loss of function mutations in the LDL receptor and follows an autosomal dominant pattern of inheritance.]]
Answer B	AnswerB::The disease is associated with subcutaneous deposits
Answer B Explanation	[[AnswerBExp::Familial hypercholesterolemia causes an increase in LDL cholesterol, which can cause subcutaneous fatty xanthomas of the Achilles tendon and xanthelasmas on the eyelids.]]
Answer C	AnswerC::The disease is associated with hepatomegaly
Answer C Explanation	[[AnswerCExp::Hyperchylomicronemia, a different dyslipidemia, is associated with hepatomegaly.]]
Answer D	AnswerD::The disease is associated with increased chylomicrons
Answer D Explanation	[[AnswerDExp::This patient has familial hypercholesterolemia (type IIa dyslipidemia), which is associated with increased levels of cholesterol in the blood. Patients with hyperchylomycronemia (type I dyslipidemia) have increased levels of serum chylomicrons.]]
Answer E	AnswerE::The disease is caused by gain-of-function mutations in HMG-CoA reductase
Answer E Explanation	[[AnswerEExp::Familial hypercholesterolemia is caused by loss-of-function mutations in the LDL receptor and follows an autosomal dominant pattern of inheritance.]]
Right Answer	RightAnswer::B
Explanation	[[Explanation::Familial hypercholesterolemia or familial dyslipidemia type IIa is an autosomal dominant genetic disorder that is characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL). Patients with the homozygous form usually have LDL levels > 700 mg/dL and have early cardiovascular disease. Many patients have mutations in the LDLR gene, which encodes the LDL receptor protein that normally eliminates LDL from the circulation. Heterozygous familial hypercholesterolemia is usually treated with statins, bile acid sequestrants, or other hypolipidemic agents that lower cholesterol levels. Individuals with homozygous mutations are more difficult to treat as these individuals lack any functional LDLR, which statins could serve to upregulate. These patients may eventually require liver transplantation. Cholesterol may be deposited on the skin, leading to the formation of xanthelasma palpebrarum, which are characterized by the formation of yellowish patches around the eyelids, and xanthomas, which are subcutaneous fatty deposits in the tendons of the hands, elbows, knees and feet, particularly at the distal one-third of the Achilles tendon. The eyes may also be involved in patients with familial hypercholesterolemia, showing arcus senilis corneae, a whitish arc at the edge of the cornea. Accelerated deposition of cholesterol in the walls of arteries leads to atherosclerosis, the underlying cause of cardiovascular disease. Patients with familial hypercholesterolemia may have premature cardiovascular disease at the age of 30 to 40. Educational Objective: Familial hypercholesterolemia causes an increase in LDL cholesterol, which can cause subcutaneous fatty xanthomas of the Achilles tendon and xanthelasmas on the eyelids. References: First Aid 2014 page 110, 118]]
Approved	Approved::Yes
Keyword	WBRKeyword::Familial hypercholesterolemia, WBRKeyword::Dysplipidemia, WBRKeyword::Lipids, WBRKeyword::Cholesterol, WBRKeyword::Heart, WBRKeyword::Cardiovascular, WBRKeyword::Genetics, WBRKeyword::Myocardial infarction, WBRKeyword::Atherosclerosis, WBRKeyword::WJG
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