WBR0986

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 3 year-old-girl is brought to the physician's office for progressively worsening hypotonia. The mother states that her daughter's condition has been associated with two previous episodes of acute-onset, self-resolving lack of coordination. The girl's height and weight are below the lower threshold of growth on the height-weight chart. Laboratory work-up is remarkable for mild metabolic acidosis. A skeletal muscle biopsy demonstrates E1 subunit deficiency in the pyruvate dehydrogenase complex. The physician advises the family to adhere to a strict diet. Which of the following amino acids should be included in this girl's diet?]]
Answer A	AnswerA::Methionine
Answer A Explanation	[[AnswerAExp::Methionine is a strictly glucogenic amino acid. A patient with pyruvate dehydrogenase deficiency is required to have a strict ketogenic diet.]]
Answer B	AnswerB::Valine
Answer B Explanation	[[AnswerBExp::Valine is a strictly glucogenic amino acid. A patient with pyruvate dehydrogenase deficiency is required to have a strict ketogenic diet.]]
Answer C	AnswerC::Isoleucine
Answer C Explanation	[[AnswerCExp::Isoleucine is a glucogenic and ketogenic amino acid. A patient with pyruvate dehydrogenase deficiency is required to have a strict ketogenic diet.]]
Answer D	AnswerD::Threonine
Answer D Explanation	[[AnswerDExp::Threonine is a glucogenic and ketogenic amino acid. A patient with pyruvate dehydrogenase deficiency is required to have a strict ketogenic diet.]]
Answer E	AnswerE::Lysine
Answer E Explanation	[[AnswerEExp::Lysine and leucine are strictly ketogenic amino acids that are not metabolized by pyruvate dehydrogenase. Patients with pyruvate dehydrogenase deficiency require strict ketogenic diet that is rich in fat and amino acids leucine and lysine.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::Pyruvate dehydrogenase (PDH) complex defects are associated with development of irritability, poor feeding, seizures, impaired psychomotor development, lactic acidosis, and elevated serum alanine concentration (accumulated pyruvate is shunted to lactate via LDH and to alanine via ALT). PDH deficiency is a genetic disorder that may be inherited in either an autosomal or X-linked pattern. This patient's diagnosis is first suspected by the findings on physical examination and lab work-up and further confirmed by genetic testing, which demonstrated E1 alpha gene defect. The majority of patients with PDH deficiency have E1 alpha gene defects (PDHA1), which are usually inherited in an X-linked pattern. Management of PDH deficiency includes a strict ketogenic diet (high intake of fat and/or ketogenic amino acids lysine and leucine). 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. The treatment of this disease is a strict ketogenic diet high in fat and in the ketogenic amino acids lysine and leucine. Glucogenic amino acids: methionine, valine Glucogenic and ketogenic amino acids: isoleucine, threonine, tryptophan and phenylalanine Ketogenic amino acids: leucine, lysine Reference: Educational Objective: The majority of patients with PDH deficiency have E1 alpha gene defects (PDHA1), which are usually inherited in an X-linked pattern. Management of PDH deficiency includes a strict ketogenic diet (high intake of fat and/or ketogenic amino acids lysine and leucine). References: Bindoff LA, Birch-Machin MA, Farnsworth L, et al. Familial intermittent ataxia due to a defect of the E1 component of pyruvate dehydrogenase complex. J Neurol Sci. 1989;93:311-8 First Aid 2014 page 103]]
Approved	Approved::No
Keyword	WBRKeyword::Pyruvate dehydrogenase, WBRKeyword::lysine, WBRKeyword::ketongenic
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::