WBR0646

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	USMLE Step 1
Main Category	Biochemistry
Sub Category	Dermatology, General Principles
Prompt	A 4-year-old girl presents to the emergency room for 2 episodes of blood in the stools. History is initially inconclusive, but further questioning reveals that the child was recently diagnosed with a rare disorder that causes her to have hyperelastic skin and hyperextensible joints. Considering this patient has a mutation in type 1 collagen, what co-factor is essential in the defective enzyme in this patient?
Answer A	Selenium
Answer A Explanation	Selenium is a known cofactor for thyroid hormone deiodinases. It has no function with lysyl-oxidase.
Answer B	Niacin
Answer B Explanation	Niacin also known as vitamin B3 is an important cofactor for hydrogen transfer processes as NAD and NADP. It has no function with lysyl-oxidase.
Answer C	Zinc
Answer C Explanation	Zinc is very important in the formation of zinc fingers which constitute parts of some transcription factors. It has no function with lysyl-oxidase.
Answer D	Copper
Answer D Explanation	Copper is important for the proper functioning of lysyl-oxidase an enzyme defective in certain forms of Ehlers-Danlos syndrome.
Answer E	Biotin
Answer E Explanation	Biotin functions as a cofactor for carboxylation reactions (Acetyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and propionyl-CoA carboxylase). It has no function with lysyl-oxidase.
Right Answer	D
Explanation	Ehlers-Danlos Syndrome is a rare inherited disease that is heterogeneous in presentation and pathologic mechanisms. Six subtypes of Ehlers-Danlos exist with each having distinct mutations affecting collagen synthesis. One of the most studied pathological mechanisms of Ehlers-Danlos is a mutation affecting lysyl-oxidase, an enzyme responsible for collagen crosslinking in the extracellular matrix. Lysyl-oxidase requires copper as a cofactor to function effectively. Ehlers-Danlos classically presents with skin hyperextensibility, cutaneous fragility, joint hypermobility, and vascular anomalies. Educational Objective: Ehlers-Danlos is a rare inherited disorder with certain forms characterized by defective corss-linking of collagen fibers due to abnormal lysyl-oxidase. Lysyl oxidase requires copper as a cofactor. References: Wenstrup RJ, Florer JB, Willing MC, et al. COL5A1 haploinsufficiency is a common molecular mechanism underlying the classical form of EDS. Am J Hum Genet. 2000;66(6):1766-76. Mao JR, Bristow J. The Ehlers-Danlos syndrome: on beyond collagens. J Clin Invest. 2001;107(9):1063-9.
Approved	Yes
Keyword	Ehlers-Danlos Syndrome, Collagen sythesis, Lysyl oxidase, Copper, Collagen, Ehlers-Danlos
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