WBR1018

Author	[[PageAuthor::Ogheneochuko Ajari, MB.BS, MS [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	USMLE Step 1
Main Category	Biochemistry
Sub Category	General Principles
Prompt	A 5-month-old boy was evaluated for poor feeding and growth, hypotonia, vomiting, lactic acidemia, and garlic breath. The ratio of pyruvate to lactate in the serum is elevated with decreased conversion of pyruvate to acetyl CoA in fibroblasts. Administration of the following compounds is recommended to manage this patient's condition?
Answer A	Pyridoxine
Answer A Explanation	[[AnswerAExp::Pyridoxine (vitamin B6) is not a co-factor of the pyruvate dehydrogenase complex. Vitamin B6 is used in transamination (e.g. ALT and AST), decarboxylation reactions, and in glycogen phosphorylase.]]
Answer B	Thiamine
Answer B Explanation	[[AnswerBExp::Thiamine is a co-factor required for the normal functioning of the pyruvate dehydrogenase complex. Administration of thiamine (vitamin B1) is usually recommended to manage patients with pyruvate dehydrogenase deficiency.]]
Answer C	Cobalamin
Answer C Explanation	[[AnswerCExp::Cobalamin (vitamin B12) is a co-factor for homocysteine methyltransferase and methylmalonyl-CoA mutase. It is not a co-factor in the pyruvate dehydrogenase complex.]]
Answer D	Biotin
Answer D Explanation	[[AnswerDExp::Biotin (vitamin B7) is a cofactor for carboxylation enzymes. It is not required in the pyruvate dehydrogenase complex.]]
Answer E	Ascorbic acid
Answer E Explanation	[[AnswerEExp::Ascorbic acid (vitamin C) is necessary for the hydroxylation of proline and lysine during collagen synthesis.]]
Right Answer	B
Explanation	[[Explanation::An elevation of pyruvate and deficiency of acetyl CoA suggest pyruvate dehydrogenase deficiency, which typically manifests in infancy with neurologic deficits, poor feeding and growth, vomiting, hypotonia, lactic acidemia, rice water stools, and garlic breath. Administration of thiamine (vitamin B1) is usually recommended to manage patients with pyruvate dehydrogenase deficiency. Thiamine is a co-factor required for the normal functioning of the pyruvate dehydrogenase complex. Other co-factors include Vitamins B2 (Riboflavin or FAD+), B3 (Niacin or NAD+), B5 (CoA or Pantothenate), and lipoic acid. Educational Objective: Thiamine is a co-factor required for the normal functioning of the pyruvate dehydrogenase complex. Administration of thiamine (vitamin B1) is usually recommended to manage patients with pyruvate dehydrogenase deficiency. References: First Aid 2015 page 89, 99.]]
Approved	Yes
Keyword	Pyruvate dehydrogenase deficiency, Garlic breath, Vitamin, Vitamin B1, Thiamine, Neurologic deficit, Inborn error of metabolism, Pyruvate, Lactate, Acetyl-CoA
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