WBR0345

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 2 year old boy is brought by his mother to the physician's office for delayed speech. The mother informs the physician that unlike his older siblings his age, the patient is very irritable and is unusually hyperactive. Further questioning reveals that the patient/s family lives in an old house that has chipped paint. Physical examination is remarkable for pallor. Complete blood count (CBC) shows hemoglobin: 9.8 g/dL and MCV: 68 fl. Peripheral smear of the patient's blood shows basophilic stippling. Based on the simplified image below, which of the following steps of heme synthesis are 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::"B" corresponds to ALA dehydratase, inhibited by lead.
Answer C	AnswerC::C
Answer C Explanation	AnswerCExp::"C" corresponds to porphobilinogen deaminase. Deficiency of this enzyme causes acute intermittent porphyria.
Answer D	AnswerD::D
Answer D Explanation	AnswerDExp::"D" corresponds to uroporphyrinogen III synthase. It is not a clinically important enzyme.
Answer E	AnswerE::E
Answer E Explanation	AnswerEExp::"E" corresponds to uroporphyrinogen decarboxylase. It is deficient in porphyria cutanea tarda.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient is most likely diagnosed with lead toxicity. Lead toxicity is not uncommon in developing countries in very young children. Patients typically present with failure to meet developmental milestones, speech delay, hyper or hypoactivity, and irritability. The patient's exposure to chipped paints in old houses (pre-1960s) puts the patient at hight risk for lead toxicity. Physical examination showing pallor is also consistent with the diagnosis. In patients with lead toxicity, work-up shows microcytic hypochromic anemia with low MCV, as shown in this patient. Additionally, peripheral smear shows basophilic stippling. Lead inhibits 2 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). Educational Objective: Lead inhibits ALA-dehydratase and ferrochelatase. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::lead, WBRKeyword::poisoning, WBRKeyword::toxicity, WBRKeyword::ALA, WBRKeyword::dehydratase, WBRKeyword::ferrochelatase, WBRKeyword::anemia, WBRKeyword::microcytic, WBRKeyword::hypochromic, WBRKeyword::basophilic, WBRKeyword::stippling, WBRKeyword::peripheral, WBRKeyword::smear, WBRKeyword::old, WBRKeyword::house, WBRKeyword::chipped, WBRKeyword::paint, WBRKeyword::irritability, WBRKeyword::speech, WBRKeyword::delay
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Order in Linked Questions	LinkedOrder::