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Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management

  • Autonomic Dysfunction (L.H. Weimer, Section Editor)
  • Published:
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A Correction to this article was published on 10 December 2020

This article has been updated

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.

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Acknowledgments

The authors thank Dr. Peter H. King, Professor of Neurology, The University of Alabama at Birmingham, for the critical revision of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, University of Alabama at Birmingham, 1720 2nd Ave. South, SC271, Birmingham, AL, 35294-0017, USA

    Mohamed Kazamel

  2. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert J. Desnick

  3. Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    John G. Quigley

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Correspondence to Mohamed Kazamel.

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Dr. Kazamel received consulting fees from Akcea Therapeutics.

Dr. Desnick is a consultant for Alnylam Pharmaceuticals and Recordati Rare Diseases. He has received grants from both entities. He receives royalties for a licensed patent to Alnylam Pharmaceuticals.

Dr. Quigley received consulting fees from Alnylam Pharmaceuticals.

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Kazamel, M., Desnick, R.J. & Quigley, J.G. Porphyric Neuropathy: Pathophysiology, Diagnosis, and Updated Management. Curr Neurol Neurosci Rep 20, 56 (2020). https://doi.org/10.1007/s11910-020-01078-8

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