Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management

Academic Article

Abstract

  • Purpose of Review: To review the peripheral neurological complications of the acute hepatic porphyrias, as well as the latest advances in their pathophysiology and management. Recent Findings: The diagnosis of porphyric neuropathy remains challenging as varying neuropathic patterns are encountered depending on disease stage, including a non-length-dependent distribution pattern. The major pathophysiologic mechanism is δ-aminolevulinic acid (ALA)–induced neurotoxicity. The less restrictive blood-nerve barrier in the autonomic ganglia and myenteric plexus may explain the frequency of dysautonomic manifestations. Recently, a prophylactic small interfering RNA (siRNA)-based therapy that reduces hepatic ALA Synthase-1 mRNA was approved for patients with recurrent neuro-visceral attacks. Summary: Neurologists should appreciate the varying patterns of porphyric neuropathy. As with most toxin-induced axonopathies, long-term outcomes depend on early diagnosis and treatment. While the short-term clinical and biochemical benefits of siRNA-based therapy are known, its long-term effects on motor recovery, chronic pain, and dysautonomic manifestations are yet to be determined.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Kazamel M; Desnick RJ; Quigley JG
  • Volume

  • 20
  • Issue

  • 12