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Retired NBME 27 Answers

nbme27/Block 1/Question#32 (reveal difficulty score)
A 30-year-old man is brought to the physician ...
Porphobilinogen deaminase ๐Ÿ” / ๐Ÿ“บ / ๐ŸŒณ / ๐Ÿ“–
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submitted by โˆ—shak360(19)
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There are three main conditions related to heme synthesis and lead poisoning:

  • Lead poisoning - affects ferrochelatase (which performs the conversion of protoporphyrin to heme) and ALA dehydratase (which performs the conversion of ALA to porphobilinogen) and as such causes the build-up of protoporphyrin and ALA. In particular, it causes neurological symptoms (mental retardation in children and headaches and memory loss in adults). It can also cause microcytic anemia (basophilic stippling in peripheral smears and ringed sideroblasts in central bone marrow smears).

  • Acute intermittent porphyria - affects porphobilinogen deaminase (which performs the conversion of porphobilinogen to hydroxymethylbilane) and results in a build-up of porphobilinogen and ALA. Most importantly, this is often precipitated by drugs that are cytochrome P-450 inducers, but also other drugs such as sulfonamides (like trimethoprim-sulfamethoxazole as in this question), barbiturates, oral contraceptives, and rifampin. This disease is also autosomal dominant, indicated by the mother and maternal grandfather having had similar presentations. Finally, porphobilinogen is neurotoxic and can cause abdominal pain, psychosis, and polyneuropathy.

  • Poryphria cutanea tarda - affects uroporphyrinogen decarboxylase (which performs the conversion of uroporphyrinogen III to coproporphyrinogen III) and results in the build-up of uroporphyrin which can be observed in tea-colored urine. This disease particularly gives patients blistering cutaneous photosensitivity and hyperpigmentation and is the most common.

  • X-linked sideroblastic anemia - affects ALA synthase. This is more importantly seen in B6 deficiencies or B6 deficiencies secondary to the use of Isoniazid, an inhibitor of the synthesis of mycolic acids in Mycobacterium tuberculosis. It can also be seen in X-linked defects in ALA synthase.

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