Review Question - QID 100072

This patient with abdominal pain, reddish-brown urine and psychological disturbances likely has acute intermittent porphyria (AIP), caused by a defect in porphobilinogen deaminase.

Acute intermittent porphyria is a rare disease characterized by abdominal pain, reddish-brown or dark urine, polyneuropathy, and psychological disturbances. The disease is caused by a defect in the heme synthesis enzyme, porphobilinogen deaminase, which leads to increased concentrations of the toxic upstream metabolites aminolevulonic acid and porphobilinogen. Attacks may be precipitated by drugs that place an increased demand on heme synthesis in the liver by inducing the cytochrome P450 system. The long list of such drugs includes alcohol, phenytoin, phenobarbitol, and griseofulvin.

Grandchamp discusses AIP. He notes that the disease is transmitted via autosomal dominant inheritance with incomplete penetrance. Estimates of prevalence vary, although individuals of Swedish descent have a much higher prevalence than the general population. Major clinical manifestations, such as abdominal pain and neurological disturbances, occur during acute attacks. Acute attacks are often precipitated by drugs, alcohol, infections or low caloric intake. Treatment with heme improves the prognosis associated with acute attacks.

Thadani et al. discuss the diagnosis and management of porphyrias. The authors note that while acute attacks associated with the seven main types of porphyria may be life-threatening, they can often be aborted by the early administration of heme arginate. Patients with acute porphyrias are often misdiagnosed due to their symptoms of abdominal pain or atypical psychiatric symptoms. Given the autosomal dominant inheritance pattern, family members of patients diagnosed with acute porphyria should be screened for the disease.

Figure A is an image of the reddish-brown colored urine that might be seen in a patient with AIP.

Incorrect Answers:
Answer 1: Pyruvate dehydrogenase is an enzyme in the glycolysis pathway that is responsible for the conversion of pyruvate to acetyl CoA + CO2 and NADH.
Answer 2: Phosphofructokinase is an enzyme in the glycolysis pathway and catalyzes one of the rate-limiting, ATP requiring steps.
Answer 3: Glucose-6-phosphatase is an enzyme in the gluconeogenesis pathway that allows for glucose to be exported from the liver into the bloodstream.
Answer 5: Defects in uroporphyrinogen decarboxylase cause porphyria cutanea tarda, a disorder in which patients blister when exposed to sun.