08-01-2007, 06:25 PM
A 26-year-old woman is brought into the emergency department with abdominal pain and hallucinations. Physical examination reveals anisocoria and decreased deep tendon reflexes. There are no photosensitive skin lesions. Urinalysis shows elevated urine porphobilinogen and delta aminolevulinic acid (δ-ALA). It is discovered that the woman was in the sun all weekend and had been taking a pain reliever/barbiturate combination prescribed for tension headache. Which of the following is the most likely diagnosis?
A. Acute intermittent porphyria
B. Congenital erythropoietic porphyria
C. Hereditary coproporphyria
D. Lead poisoning
E. Porphyria cutanea tarda
The correct answer is A. Porphyrias are caused by inherited or acquired deficiencies in heme synthesis, resulting in an accumulation of porphyrins or porphyrin precursors. Acute intermittent porphyria is caused by a deficiency in uroporphyrinogen I synthase. As a result, porphobilinogen and δ-ALA accumulate in the urine. Patients often present with abdominal pain and neuropsychiatric disturbances. Lack of photosensitive lesions distinguishes this porphyria from other defects in heme biosynthesis. In these other porphyrias, accumulation of tetrapyrrole intermediates increases the formation of superoxide radicals in response to UV light. As a result, there is oxidative damage to membranes and release of destructive lysosomal enzymes causing photosensitivity. An acute attack is often precipitated by sun exposure and drugs that induce the synthesis of P450 microsomal enzymes, such as barbiturates. In response to barbiturates, the synthesis of cytochrome P450 increases, leading to an enhanced consumption of heme. This, in turn, causes a decrease in hepatic heme concentration. The lower intracellular heme concentration activates ALA synthase and promotes the synthesis and accumulation of precursors before the enzyme block.
A. Acute intermittent porphyria
B. Congenital erythropoietic porphyria
C. Hereditary coproporphyria
D. Lead poisoning
E. Porphyria cutanea tarda
The correct answer is A. Porphyrias are caused by inherited or acquired deficiencies in heme synthesis, resulting in an accumulation of porphyrins or porphyrin precursors. Acute intermittent porphyria is caused by a deficiency in uroporphyrinogen I synthase. As a result, porphobilinogen and δ-ALA accumulate in the urine. Patients often present with abdominal pain and neuropsychiatric disturbances. Lack of photosensitive lesions distinguishes this porphyria from other defects in heme biosynthesis. In these other porphyrias, accumulation of tetrapyrrole intermediates increases the formation of superoxide radicals in response to UV light. As a result, there is oxidative damage to membranes and release of destructive lysosomal enzymes causing photosensitivity. An acute attack is often precipitated by sun exposure and drugs that induce the synthesis of P450 microsomal enzymes, such as barbiturates. In response to barbiturates, the synthesis of cytochrome P450 increases, leading to an enhanced consumption of heme. This, in turn, causes a decrease in hepatic heme concentration. The lower intracellular heme concentration activates ALA synthase and promotes the synthesis and accumulation of precursors before the enzyme block.