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NBME 21 Answers

nbme21/Block 1/Question#41

A 35-year-old woman comes to the physician because ...

Uroporphyrinogen decarboxylase

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 +4  upvote downvote
submitted by neonem(298),

This is a case of porphyria cutanea tarda. The way I remember this is that it's the only high-yield porphyria that has skin manifestations due to UV. I remember this by "After U (uroporphyrin), it's UV". Apparently it's also associated with Hepatitis C, which could be the reason why there's increased AST & ALT, or it could be due to toxic buildup of intermediates in heme synthesis.

meningitis  Why cant it be protoporphyrinogen oxidase? It was because of that reason (Increased AST and ALT) I thought it wasnt uroporphyrinogen decarb. My train of thought was: "wow, mitochondria are messed up.. there must be a lot of intermediates in there,therefore the Uroporph decarb must OK." +  
arlenieeweenie  FA 2019 pg. 417, the later on the defect in the heme synthesis pathway is the one more associated with skin findings! Also according to this year's edition uroporphyrinogen synthase is now known as prophobilinogen deaminase +  

 +1  upvote downvote
submitted by divya(8),

The porphyrinogens following PBG conversion into Uroporphryinogen 3 cause photosensitivity because ONLY these react with oxygen on excitation by UV light.

Therefore deficiency of any of the following enzymes -

uroporphyrinogen decarboxylase coproporphyrinogen oxidase, proporphyrinogen oxidase and ferrrochelatase can cause photosensitivity.

But between answer choices B & C, C is right because of it's association with Hep C, raised AST ALT as @neonem said.

 +0  upvote downvote
submitted by h0odtime(2),

Heme Mnemonics

  • Sideroblastic Anemia - ALAS (Ends in S = Sideroblastic)
  • Lead Poisoning - ALAD & Ferrochelatase. (ALeAD, FerrocheLEADtase)
  • Cytoplasmic Intermediates: Purposefully (PBD) Hold 3Urine (UPD) Cups
  • Porphobilinogen PBD → Hydroxymethylbilane → Uroporphyrinogen 3 UPD → Copropohyrinogen 3

 +0  upvote downvote
submitted by nwinkelmann(134),

If you struggle with Biochem and haven't heard of Moof Universitry, I would highly recommend checking it out. The below information I got from this video: https://courses.moofuniversity.com/courses/take/medical-biochemistry-for-usmle-step-1-exam/lessons/4363869-porphyrias-porphyria-cutanea-tarda-pct and it's great.

Porphryia cutanea tarda = AD mutation of uroporphyrinogen decarboxylase, this is the MCC of porphyria, and it presents in 40s-50s.

Main symptom of photosensitivity leading to skin lesions/blisters/bullae due to skin porphyrinogens being oxidized by light to prophryins that damage the skin, and other skin findings of hypertrichosis/hyperpigmentation.

A key feature is possible liver problems due to associated precipitating factors. MCC precipitating factors = excessive EtOH and OCPs because of CYP450 inducers reducing serum heme levels to be utilized in the new CYP450 enzymes, thus stimulating ALA synthase due to decreased heme inhibition. Other precipitating factors include viral hepatitis, especially hepatitis C, and excess iron as in hemochromatosis. These can lead to elevated AST and ALT levels.

Another sign is dark "port-wine" colored urine which pink fluoresces under Wood light. Absent symptoms = abdominal pain and CNS problems because ALA and PBG do not accumulate. Accumulated products = uroporphyrin III, uroporphyrinogen III, uroporphyrin I, and uroporphyrinogen I.

Treatment = sun exposure avoidance, removal of precipitating factors, phlebotomy, chloroquine (which can bind and lead to excretion of accumulations). Prognosis = excellent.