WBR0983

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::An 18 months old boy was noted to have recurrent episodes of ptosis and swallowing difficulty. The episodes last for a couple of days and recur approximately every couple of months. The boy was normal at birth but has had generalized hypotonia throughout his development. Laboratory evaluation reveals lactic acidosis. Genetic studies reveal a defect in the E-1 alpha gene confirming the diagnosis of the patient. Counseling is provided for the parents who were instructed to strictly provide their son with a ketogenic diet. Defect in which of the following enzymes is most likely implicated in this patient's condition?]]
Answer A	AnswerA::Acyl-co dehydrogenase
Answer A Explanation	[[AnswerAExp::Acyl-co dehydrogenase is involved in the fatty acid metabolism. Deficiency in acyl-co A dehydrogenase leads to elevated levels of dicarboxylic acid and decreased levels of glucose and ketones. The defect in the E-1 alpha gene points towards the diagnosis of pyruvate dehydrogenase deficiency.]]
Answer B	AnswerB::Alpha ketoglutarate dehydrogenase
Answer B Explanation	[[AnswerBExp::Alpha ketoglutarate dehydrogenase is involved in Krebs cycle. The defect in the E-1 alpha gene in this patient points towards the diagnosis of pyruvate dehydrogenase deficiency and not alpha ketoglutarate dehydrogenase deficiency.]]
Answer C	AnswerC::Pyruvate dehydrogenase
Answer C Explanation	[[AnswerCExp::Pyruvate dehydrogenase links glycolysis to Krebs cycle. Pyruvate dehydrogenase is associated with the accumulation of pyruvate and alanine as well as with lactic acidosis as seen in this patient. The defect in the E-1 alpha gene points towards the diagnosis of pyruvate dehydrogenase deficiency.]]
Answer D	AnswerD::Branched-chain alpha ketodehydrogenase
Answer D Explanation	[[AnswerDExp::Branched-chain alpha ketodehydrogenase is involved in the breakdown of branched amino acids such as leucine, isoleucine and lysine. Deficiency in branched-chain alpha ketodehydrogenase is the underlying cause of maple syrup disease. The defect in the E-1 alpha gene in this patient points towards the diagnosis of pyruvate dehydrogenase deficiency.]]
Answer E	AnswerE::Lactate dehydrogenase
Answer E Explanation	AnswerEExp::The defect in the E-1 alpha gene points towards the diagnosis of pyruvate dehydrogenase deficiency and not lactate dehydrogenase.
Right Answer	RightAnswer::C
Explanation	[[Explanation::This boy presents with neurological symptoms since infancy in the context of lactic acidosis. The defect in the E-1 alpha gene points towards the diagnosis of pyruvate dehydrogenase deficiency which is mostly an X-linked disease. There are two main types of presentations of pyruvate dehydrogenase deficiency: a metabolic presentation characterized by severe lactic acidosis at birth, or a chronic neurological presentation characterized by hypotonia, lethargy and mental retardation. The treatment of this disease is a strict ketogenic diet high in fat and in the ketogenic amino acids lysine and leucine. Pyruvate dehydrogenase is also thiamine responsive. Educational objective: Pyruvate dehydrogenase deficiency is an X-linked disease caused by a mutation in the E1 alpha subunit of the pyruvate dehydrogenase complex leading to metabolic acidosis and neurological symptoms. Reference: de Meirleir, L., Specola, N., Seneca, S., Lissens, W. Pyruvate dehydrogenase E1-alpha deficiency in a family: different clinical presentation in two siblings. J. Inherit. Metab. Dis. 21: 224-226, 1998. Brown, G. K., Otero, L. J., LeGris, M., Brown, R. M. Pyruvate dehydrogenase deficiency. J. Med. Genet. 31: 875-879, 1994. First aid for USMLE step 1, 2013. Page 101. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Pyruvate dehydrogenase
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::