title: Role of delta-aminolevulinic acid in the symptoms of acute porphyria.
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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco. Electronic address: montgomery.bissell@ucsf.edu.
authors.forename: D Montgomery
authors.initials: DM
authors.lastname: Bissell
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of California, San Francisco.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Lai
authors.affiliation: Occupational Lead Poisoning Prevention Program, California Department of Public Health, Richmond.
authors.forename: Raymond K
authors.initials: RK
authors.lastname: Meister
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Blanc
mesh_terms: D015746:Abdominal Pain / Q000209:etiology / Q000378:metabolism; D000328:Adult; D000622:Aminolevulinic Acid / Q000097:blood / Q000652:urine; D015913:Chelation Therapy / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D007855:Lead Poisoning / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D008515:Medicine, Ayurvedic; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis*; D016896:Treatment Outcome; D020176:Tyrosinemias / Q000175:diagnosis*
chemical_list: D006418:Heme; D000622:Aminolevulinic Acid
keywords: Abdominal pain; Acute porphyria; Ayurveda; Delta-aminolevulinic acid; Lead poisoning