WBR0646
| Author | [[PageAuthor::Rim Halaby, M.D. [1]]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry |
| Sub Category | SubCategory::Dermatology, SubCategory::General Principles |
| Prompt | [[Prompt::A 4 year old girl presents to the emergency room for 2 episodes of blood in the stools. History initially is inconclusive, but upon further questioning the mother explains that her child was recently diagnosed with a rare disorder that causes her to have very stretchy skin, and joints that can extend beyond the normal range. Considering this patient has a mutation in type 1 collagen, what co-factor is essential in the defective enzyme in this patient?]] |
| Answer A | AnswerA::Selenium |
| Answer A Explanation | AnswerAExp::Selenium is a known cofactor for thyroid hormone deiodinases. It has no function with lysyl-oxidase. |
| Answer B | AnswerB::Niacin |
| Answer B Explanation | AnswerBExp::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 | AnswerC::Zinc |
| Answer C Explanation | AnswerCExp::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 | AnswerD::Copper |
| Answer D Explanation | AnswerDExp::Copper is important for the proper functioning of lysyl-oxidase an enzyme defective in certain forms of Ehlers-Danlos syndrome. |
| Answer E | AnswerE::Biotin |
| Answer E Explanation | AnswerEExp::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 | RightAnswer::D |
| Explanation | [[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. The classical types of Ehlers-Danlos involve mostly collagen type 1 and collagen type 4. 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.Mutations often involve the COL-A genes.
Reference: 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 | Approved::No |
| Keyword | WBRKeyword::Ehlers-Danlos Syndrome, WBRKeyword::Collagen sythesis, WBRKeyword::Lysyl oxidase, WBRKeyword::Copper |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |