Rare diseases Xagena

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Delta-aminolevulinic acid synthase-1 is a target for additional therapies to control symptoms in acute porphyria

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.

Researchers have reviewed genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a similar pain syndrome.

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.

In 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. ( Xagena )

Bissell DM et al, Am J Med 2015;128:313-317