Porphobilinogen deaminase, deficiency

R.L.P. Lindberg, C. Procher, B. Grandchamp, B. Lederman, K. Burki, S. Aguzzi, U.A. Meyer (1996). Porphobilinogen deaminase deficiency in mice causes a neuropathy resembling that of human hepatic porphyria. Nat. Gen., 12, 195-199. 

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Acute intermittent porphyria is a severe form of porphyria which is due to a deficiency of porphobilinogen deaminase (hydroxymethylbilanesynthase). 

Acute intermittent porphyria is associated with excessive urinary excretion of ALA and porphobilinogen. The lack of polymerization of porphobilinogen is due to deficiency of porphobilinogen deaminase in several cell types (e.g., hepatocytes, erythrocytes, fibroblasts, lymphocytes). Acute clinical manifestations include neuropsychiatric disorders and abdominal pain. The cause of these manifestations is not clear, but accumulation of porphyrin precursors (ALA and porphobilinogen) in pharmacological amounts has been implicated. Since afflicted subjects cannot make porphyrins to any great extent, they are not photosensitive. This disorder is inherited as an autosomal dominant trait. 

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