Role of delta-Aminolevulinic Acid in the Symptoms of Acute Porphyria
Authors
D MD
Division of Gastroenterology, Department of Medicine, University of California, San Francisco
Jennifer MD
Division of Gastroenterology, Department of Medicine, University of California, San Francisco
Raymond MPH
Occupational Lead Poisoning Prevention Program, California Department of Public Health, Richmond, California
Paul MSPH
Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco
Keywords:
Acute porphyria, abdominal pain, delta-aminolevulinic acid, lead poisoning, Ayurveda
Abstract
Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and are accompanied by overproduction of heme-precursor molecules, specifically delta-aminolevulinic acid and porphobilinogen. The basis for the acute symptoms in these diseases has been speculative.
Methods
We review genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a very similar pain syndrome.
Results
While each of these conditions has characteristic urine biochemistry, all exhibit excess delta-aminolevulinic acid. Moreover, in all, treatment with hemin reduces delta-aminolevulinic acid and relieves symptoms. In contrast, use of recombinant porphobilinogen deaminase to knock down porphobilinogen in acute porphyria was ineffective.
Conclusion
There is now convincing evidence that delta-aminolevulinic acid is the cause of pain in the acute porphyrias. The efficacy of hemin infusion is due mainly, if not entirely, to its inhibition of hepatic delta-aminolevulinic acid synthase-1, the enzyme that catalyzes delta-aminolevulinic acid formation. Delta-aminolevulinic acid synthase-1 is a rational target for additional therapies to control symptoms in acute porphyria.
Keywords: Acute porphyria, abdominal pain, delta-aminolevulinic acid, lead poisoning, Ayurveda
Click on "Archives" to access the full archive of scientific preprints. You may use the categories and the search functionality to find select preprints you're interested in.
