Format

Send to

Choose Destination
Am J Med. 2015 Mar;128(3):313-7. doi: 10.1016/j.amjmed.2014.10.026. Epub 2014 Nov 8.

Role of delta-aminolevulinic acid in the symptoms of acute porphyria.

Author information

1
Division of Gastroenterology, Department of Medicine, University of California, San Francisco. Electronic address: montgomery.bissell@ucsf.edu.
2
Division of Gastroenterology, Department of Medicine, University of California, San Francisco.
3
Occupational Lead Poisoning Prevention Program, California Department of Public Health, Richmond.
4
Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco.

Abstract

BACKGROUND:

Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and 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 similar pain syndrome.

RESULTS:

Although 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.

CONCLUSIONS:

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:

Abdominal pain; Acute porphyria; Ayurveda; Delta-aminolevulinic acid; Lead poisoning

PMID:
25446301
PMCID:
PMC4339446
DOI:
10.1016/j.amjmed.2014.10.026
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center