WBR0469

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Gastrointestinal
Prompt	[[Prompt::An 6-month-old boy is brought by his mother to the pediatrician's office for failure to thrive, persistent diarrhea, and steatorrhea. Peripheral blood smear reveals acanthocytosis with undetectable plasma cholesterol and triglyceride. Which of the following disorders is the primary defect in this patient's condition?]]
Answer A	AnswerA::Defect in LDL receptors
Answer A Explanation	[[AnswerAExp::A defect in LDL receptors frequently results in familial hypercholesterolemia (FH).]]
Answer B	AnswerB::Defect in apolipoprotein B
Answer B Explanation	[[AnswerBExp::Although apo-B synthesis is affected in individuals with abetalipoproteinema, an apo-B defect is not the primary detect that leads to abetalipoproteinema.]]
Answer C	AnswerC::Defect in microsomal triglyceride transfer protein
Answer C Explanation	[[AnswerCExp::A defect in the MTP gene results in abetalipoproteinemia.]]
Answer D	AnswerD::Defect in lipoprotein lipase
Answer D Explanation	[[AnswerDExp::A defect in lipoprotein lipase (LPL) results in chylomicronemia]]
Answer E	AnswerE::Defect in chylomicron
Answer E Explanation	[[AnswerEExp::A defect in chylomicron is not the primary defect in individuals with abetalipoproteinemia, but often it occurs secondary to an MTP gene defect.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Abetalipoproteinemia is a rare autosomal recessive genetic disease characterized by fat accumulation in enterocytes, fat malabsorption, acanthocytosis, and hypocholesterolemia. Abetalipoproteinemia is caused by mutations in the MTP gene (long arm of chromosome 4) that encodes microsomal triglyceride transfer protein (MTP or MTTP). MTPs are required for the synthesis and post-translational processing of apo-B. As such, abetalipoproteinemia is marked by the complete absence of apo-B-containing lipoproteins, namely VLDL, LDL, and chylomicrons. At older age, abetalipoproteinemia frequently manifests with clinical signs and symptoms associated with fat-soluble vitamin deficiency. Patients often present with complaints related to the GI (steatorrhea and fat malabsorption), ocular (atypical retinitis pigmentosa), hematological (coagulopathy), and neurological (posterior column neuropathy) systems. Educational Objective: Abetalipoproteinemia results from a genetic mutation in the MTP gene. References: Aggerbeck LP, Bouma ME, Eisenberg C, et al. Absence of microsomal transfer protein in individuals with abetalipoproteinemia. Science. 1992;258(5084):999-1001. Zamel R, Khan R, Pollex RL, et al. Abetalipoproteinemia: two case reports and literature review. Orphanet J Rare Dis. 2008;3:19. First Aid 2014 page 353]]
Approved	Approved::Yes
Keyword	WBRKeyword::Abetalipoproteinemia, WBRKeyword::Malabsorption, WBRKeyword::Diarrhea, WBRKeyword::Microsomal triglyceride transfer protein, WBRKeyword::Apolipoprotein, WBRKeyword::MTP, WBRKeyword::MTTP, WBRKeyword::Apo-B, WBRKeyword::Acanthocytosis
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