WBR0126
| Author | PageAuthor::Mahmoud Sakr M.D. (Reviewed by William J Gibson) |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Biochemistry |
| Sub Category | SubCategory::General Principles |
| Prompt | [[Prompt::A 6-year-old male child is brought by his mother for medical evaluation. His mother states that her child has developed multiple blood clots in his legs and bone fractures of his limbs in the past. He has missed several developmental milestons and ophthalmology exam reveals sublaxated lens of the right eye. Which of the following is the most likely diagnosis?]] |
| Answer A | AnswerA::Marfan syndrome |
| Answer A Explanation | [[AnswerAExp::Homocystinuria and Marfan's syndrome have overlapping symptoms, including tall stature, subluxation of the lens and kyphosis. However, homocysteinuria is associated with mental retardation, osteoporosis and thrombosis while Marfan syndrome is not.]] |
| Answer B | AnswerB::Cystathionine beta-synthase deficiency |
| Answer B Explanation | [[AnswerBExp::Homocystinuria is an inherited metabolic disorder in methionine metabolism. Homocystinuria is caused by cystathionine beta synthase deficiency.]] |
| Answer C | AnswerC::Vitamin B12 deficiency |
| Answer C Explanation | [[AnswerCExp::Because Vitamin B12 is a cofactor in the conversion of homocysteine to methionine by methionine synthase, B12 deficiency can cause elevated homocysteine levels. However, B12 deficiency would not present as such a severe "classic" homocystinuria in this way. Vitamin B12 deficiency causes macrocytic anemia and subacute combined degeneration.]] |
| Answer D | AnswerD::Folic acid deficiency |
| Answer D Explanation | AnswerDExp::Folate deficiency causes a macrocytic anemia and elevated homocysteine levels. However, folate deficiency would not cause a phenotype as sever as the classic homocystinuria phenotype in this patient. |
| Answer E | AnswerE::Riboflavin deficicency |
| Answer E Explanation | [[AnswerEExp::Riboflavin (Vitamin B2) deficiency causes [cheilosis] and corneal vascularization (bloodshot eyes).]] |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::Homocystinuria is an inherited metabolic disorder in which the amino acid homocysteine accumulates to toxic levels in the blood. Elevated levels of homocysteine in the blood are primarily associated with an increased risk of atherosclerosis and thrombosis. Because patients with homocystinuria tend to be taller, have subluxation of the lens and kyphosis, they may sometimes be confused for Marfan syndrome patients. In contrast to homocystinuria, Marfan syndrome patients do not tend to develop intellectual disability or osteoporosis. Thus, both the mental retardation and bone fractures in this child suggests homocysteinuria over Marfan syndrome. While it is rare for venous thrombosis to occur in such a young child, homocysturinia can be distinguished from Marfan syndrome by an increased risk of thrombosis. Finally, recall that homocystinuria is an autosomal recessive disease and Marfan syndrome is autosomal dominant. While Marfan syndrome can occur de novo, the absence of a family history of similar symptoms supports the diagnosis of homocysteinuria over Marfan syndorme.
There are several possible genetic causes of homocystinuria including mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC genes. Only Cystathione synthase (CBS gene) mutations are high yield. Two of the notable causes are:
Educational Objective: Homocystinuria is caused by cystathionine beta synthase deficiency. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Homocystinuria, WBRKeyword::marfan syndrome, WBRKeyword::cystathionine beta synthase deficiency |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |