ABSTRACT
Four types of hepatic porphyria (acute intermittent porphyria; hereditary coprophorphyria;
variegate porphyria; delta-aminolevulinate dehydratase deficiency porphyria) present
clinically with an identical neurological syndrome. Symptoms include severe abdominal
pain, vomiting, constipation, hypertension, tachycardia, and bladder dysfunction.
These symptoms have been ascribed to autonomic neuropathy. Other symptoms are motor
weakness and sensory involvement, which correlate with peripheral axonal neuropathy,
and mental symptoms occurring without clear morphological findings in the cerebrum.
The pathogenetic mechanisms which lead to the neurological dysfunction have remained
poorly understood, partly due to the lack of a suitable animal model of these rare
disorders. Two hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA)
and heme deficiency in nervous tissue are discussed and corresponding data from porphobilinogen-deaminase
deficient mice are presented. The present evidence suggests that multiple mechanisms
interact in causing the varied symptoms, including ALA interaction with GABA receptors,
altered tryptophan metabolism, and possibly heme depletion in nerve cells.
KEY WORDS
porphyric neuropathy - mouse model of acute porphyria - pathogenesis
