A 22-year-old man comes to the office due to recurrent blistering on the back of his hands and forearms for the past several years. The patient usually develops small itchy spots but lately has had large blisters that heal with hyperpigmentation after rupturing. He has used over-the-counter topical hydrocortisone and emollients, but the symptoms have not improved. The patient works as a night security guard and has had no exposure to chemicals or animals. He drinks 2-3 cans of beer daily. Physical examination shows vesicles and erosions on the dorsum of both hands. Which of the following enzymes is most likely deficient in this patient?

Question

A 22-year-old man comes to the office due to recurrent blistering on the back of his hands and forearms for the past several years.  The patient usually develops small itchy spots but lately has had large blisters that heal with hyperpigmentation after rupturing.  He has used over-the-counter topical hydrocortisone and emollients, but the symptoms have not improved.  The patient works as a night security guard and has had no exposure to chemicals or animals.  He drinks 2-3 cans of beer daily.  Physical examination shows vesicles and erosions on the dorsum of both hands.  Which of the following enzymes is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_36e8_7ca9_9249_91df3e3c364e_MD0001_00 This patient most likely has porphyria cutanea tarda (PCT), the most common disorder of porphyrin (eg, heme) synthesis. Enzyme deficiencies in the early steps in porphyrin synthesis cause abdominal pain and neuropsychiatric manifestations (due to metabolite buildup) without photosensitivity. Late step (ie, following porphobilinogen [PBG] conversion) derangements (eg, PCT) cause photosensitivity, which is thought to be due to the accumulation of porphyrinogens that react with oxygen on excitation by ultraviolet (sun) light. PCT is caused by uroporphyrinogen decarboxylase (UROD) deficiency, which is either inherited or (more commonly) acquired, manifesting in the presence of iron and of susceptibility factors (eg, alcohol [as in this patient], smoking, halogenated hydrocarbons, hepatitis C, HIV). Photosensitivity presents as vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema. Deficiencies in coproporphyrinogen oxidase, protoporphyrinogen oxidase, or ferrochelatase can also result in photosensitivity. (Choices A and D) Deficiencies in aminolevulinate (ALA) dehydratase and PBG deaminase do not result in photosensitivity because the metabolites that accumulate are not porphyrinogens or porphyrins. PBG deaminase deficiency is seen with acute intermittent porphyria (classically presenting with abdominal pain and neuropsychiatric manifestations). (Choice B) Deficiency of ALA synthase will result in a decrease in formation of all porphyrins. This deficiency will not result in porphyria but will lead to a decrease in heme synthesis and concurrent hypochromic, microcytic anemia. Pyridoxal phosphate (vitamin B₆) is the cofactor required for activity of ALA synthase; therefore, pyridoxine deficiency can result in microcytic hypochromic anemia. (Choice C) Bilirubin glucuronyl transferase is a hepatic enzyme responsible for the conjugation of bilirubin with glucuronide, improving solubility for biliary excretion. A decrease in glucuronyl transferase results in unconjugated hyperbilirubinemia. Educational objective: Enzyme deficiencies of the early steps in porphyrin synthesis cause neuropsychiatric manifestations without photosensitivity, whereas late step derangements lead to photosensitivity. Photosensitivity manifests as vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema.

A 22-Year-Old Man Comes to the Office Due to Recurrent