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

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

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / metabolism
  • Adult
  • Aminolevulinic Acid* / blood
  • Aminolevulinic Acid* / urine
  • Chelation Therapy / methods*
  • Diagnosis, Differential
  • Female
  • Heme / biosynthesis*
  • Humans
  • Lead Poisoning* / diagnosis
  • Lead Poisoning* / etiology
  • Lead Poisoning* / metabolism
  • Lead Poisoning* / physiopathology
  • Lead Poisoning* / therapy
  • Medicine, Ayurvedic*
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Porphyria, Acute Intermittent / diagnosis*
  • Treatment Outcome
  • Tyrosinemias / diagnosis*

Substances

  • Heme
  • Aminolevulinic Acid