WBR0345
| Author | [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Alison Leibowitz)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pathophysiology |
| Sub Category | SubCategory::Hematology |
| Prompt | [[Prompt::A 2-year-old male is brought by his mother to the physician's office for delayed speech. The mother informs you that, unlike his older siblings at his age, the patient is irritable and hyperactive. Further questioning reveals that the patient's family lives in an old house with chipped paint. Physical examination is remarkable for pallor. Complete blood count (CBC) demonstrates hemoglobin levels of 9.8 g/dL and MCV: 68 fl. A peripheral smear of the patient's blood displays basophilic stippling. Based on the simplified diagram of heme synthesis shown below, which of the following steps is most likely inhibited in this patient?
|
| Answer A | AnswerA::A |
| Answer A Explanation | AnswerAExp::"A" corresponds to ALA-synthase, inhibited by B6 deficiency and in hereditary conditions, such as X-linked ALA-synthase deficiency. |
| Answer B | AnswerB::B |
| Answer B Explanation | AnswerBExp::See explanation. |
| Answer C | AnswerC::C |
| Answer C Explanation | AnswerCExp::"C" corresponds to porphobilinogen deaminase. Deficiency of this enzyme typically causes acute intermittent porphyria. |
| Answer D | AnswerD::D |
| Answer D Explanation | [[AnswerDExp::"D" corresponds to uroporphyrinogen III synthase. Uroporphyrinogen III synthase deficiency is associated with Gunther's disease.]] |
| Answer E | AnswerE:: |
| Answer E Explanation | AnswerEExp::"E" corresponds to uroporphyrinogen decarboxylase, which is typically deficient in porphyria cutanea tarda. |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::The patient in this scenario is most likely experiencing lead toxicity. Lead toxicity in young children is common in developing countries. Patients typically present with failure to meet developmental milestones, speech delay, hyper- or hypoactivity, and irritability. The patient's exposure to chipped paint in his old house (pre-1960s) increases his risk for lead toxicity. In patients with lead toxicity, work-up typically demonstrates microcytic hypochromic anemia with low MCV levels and a peripheral smear displays basophilic stippling.
Lead inhibits two enzymes of heme synthesis: ALA-dehydratase (the second step of heme synthesis) and ALA-ferrochelatase (the last step of heme synthesis). (To note, the image above is simplified. Some intermediate products and enzymes are not listed in this illustration of heme synthesis). |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::lead poisoning, WBRKeyword::lead toxicity, WBRKeyword::ALA, WBRKeyword::dehydratase, WBRKeyword::ferrochelatase, WBRKeyword::anemia, WBRKeyword::microcytic, WBRKeyword::hypochromic, WBRKeyword::basophilicstippling, WBRKeyword::peripheral smear, WBRKeyword::old, WBRKeyword::irritability, WBRKeyword::speech delay |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |
