WBR0982

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A 4-day-old newborn is brought to the emergency department (ED) for convulsions. The mother states that her baby is a product of an uneventful vaginal delivery, and his neonatal course prior to presentation was normal. She delivered the baby in a rural village abroad and returned to the United States only one day ago. She received all her prenatal vitamins and had regular follow-ups with her obstetrician during pregnancy. In the ED, the patient's vital signs are normal, and on physical examination, he appears lethargic and exhibits a stereotyped bicycling movement. The physician notes a distinctive honey-like odor of his diapers. Deficiency of which of the following enzymes is responsible for this patient's condition?]]
Answer A	AnswerA::Acyl-CoA dehydrogenase
Answer A Explanation	[[AnswerAExp::Acyl-CoA dehydrogenase is involved in fatty acid metabolism.]]
Answer B	AnswerB::Lactate dehydrogenase
Answer B Explanation	AnswerBExp::Lactate dehydrogenase catalyzes the conversion from lactate to pyruvate.
Answer C	AnswerC::Alpha-keto acid dehydrogenase
Answer C Explanation	[[AnswerCExp::Alpha-keto acid dehydrogenase is involved in the breakdown of branched amino acids (leucine, isoleucine and valine). MSUD is caused by deficiency of alpha-keto acid dehydrogenase.]]
Answer D	AnswerD::Pyruvate dehydrogenase
Answer D Explanation	[[AnswerDExp::Pyruvate dehydrogenase links glycolysis to Krebs cycle. Pyruvate dehydrogenase deficiency is associated build-up of pyruvate and alanine as well as with lactic acidosis.]]
Answer E	AnswerE::Alpha-ketoglutarate dehydrogenase
Answer E Explanation	[[AnswerEExp::Alpha ketoglutarate dehydrogenase is involved in Krebs cycle.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increase, and the disease typically manifests during the 2nd or 3rd day of birth. Manifestations include irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may also exhibit stereotyped movements referred to as fencing or bicycling. If left untreated, patients die by the 10th day of birth from ketoacidosis and respiratory failure. The diagnosis of MSUD is confirmed by elevated urinary concentrations of branched-chain amino acid, hydroxyacid, and keto acid. In USA, newborn screening for MSUD is necessary for early treatment and prevention of complications. Management of MSUD involves thiamine supplementation (thiamine is a cofactor for alpha-keto acid dehydrogenase) and dietary restrictions, where patients are advised to avoid foods with branched-chain amino acids. Educational Objective: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increases, and patients initially manifest the disease during the 2nd or 3rd day or birth. The disease typically manifests with irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may exhibit stereotyped movements referred to as fencing or bicycling. References: Strauss KA, Puffenberger EG, Morton DH. Maple Syrup Urine Disease. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2006. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1319/ First Aid 2014 page 112]]
Approved	Approved::Yes
Keyword	WBRKeyword::Maple syrup urine disease, WBRKeyword::Enzyme, WBRKeyword::Alpha-keto acid dehydrogenase, WBRKeyword::Autosomal recessive, WBRKeyword::Ketoacidosis, WBRKeyword::Convulsions, WBRKeyword::Newborn screening
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