View source for WBR0096

{{WBRQuestion
|QuestionAuthor=William J Gibson
|ExamType=USMLE Step 1
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|SubCategory=Cardiology
|MainCategory=Genetics
|MainCategory=Genetics
|SubCategory=Cardiology
|Prompt=A 20 year old male presents to the emergency room with the sudden onset of severe substernal chest pain.  His EKG shows ST segment elevation in leads V1-V4.  He denies recent physical trauma and illicit drug use.  The patient has an otherwise normal medical history. Laboratory values show elevated troponin, normal CK-MB, LDL of 340 and HDL of 30.  Which of the following is most likely true of this patient’s condition?
|Explanation=Explanation:  The patient in this vignette most likely suffers from familial hypercholesterolemia.  Familial hypercholesterolemia is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein(LDL, "bad cholesterol"), in the blood and early cardiovascular disease. Many patients have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation. Heterozygous FH is normally treated with statins, bile acid sequestrants or other hypolipidemic agents that lower cholesterol levels.  Cholesterol may be deposited in various places in the body that are visible from the outside, such as in yellowish patches around the eyelids (xanthelasma palpebrarum), the outer margin of the iris (arcus senilis corneae) and in the form of lumps in the tendons of the hands, elbows, knees and feet, particularly the Achilles tendon (tendon xanthoma).  Accelerated deposition of cholesterol in the walls of arteries leads to atherosclerosis, the underlying cause of cardiovascular disease.  These individuals may have premature cardiovascular disease at the age of 30 to 40.

References: First Aid 2012 page 90,121

|AnswerA=Follows autosomal recessive inheritance
|AnswerAExp=Incorrect - familial hypercholesterolemia is caused by loss of function mutations in the LDL Receptor and follows an autosomal dominant pattern of inheritance.
|AnswerB=Associated with achilles tendon xanthomas
|AnswerBExp=Correct - Familial hypercholesterolemia causes increased cholesterol in the blood which can cause subcutaneous deposits in the achilles tendon and eyelid in particular.
|AnswerC=Associated with hepatosplenomegaly
|AnswerCExp=Incorrect - This is true of hyperchylomicronemia, a separate dyslipidemia.
|AnswerD=Associated with increased chylomicrons
|AnswerDExp=Incorrect - Familial hypercholesterolemia (Type IIa dyslipidemia) is associated with increased levels of cholesterol in the blood.
|AnswerE=Caused by gain of function mutations in HMG-CoA reductase
|AnswerEExp=Incorrect - familial hypercholesterolemia is caused by loss of function mutations in the LDL Receptor and follows an autosomal dominant pattern of inheritance.
|RightAnswer=B
|Approved=Yes
}}