Brain Advance Access originally published online on July 17, 2008 Brain 2008 131(9):2510-2519; doi:10.1093/brain/awn152
Nerve function and dysfunction in acute intermittent porphyria
http://brain.oxfordjournals.org/cgi/content/short/131/9/2510
Nerve function and dysfunction in acute intermittent porphyria
http://brain.oxfordjournals.org/cgi/content/short/131/9/2510
Cindy S.-Y. Lin1,2,3, Arun V. Krishnan1,2, Ming-Jen Lee4, Alessandro S. Zagami1, Hui-Ling You4, Chih-Chao Yang4, Hugh Bostock5 and Matthew C. Kiernan1,2
1Prince of Wales Clinical School, 2Prince of Wales Medical Research Institute, 3School of Medical Sciences, University of New South Wales, Randwick, Sydney, New South Wales, Australia, 4Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan and 5Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, Queen Square, London, UK
Correspondence to: Matthew C. Kiernan, Associate Professor, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, New South Wales 2031, Australia E-mail: m.kiernan@unsw.edu.au
Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by mutations of the porphobilinogen deaminase gene. Clinical manifestations of AIP are caused by the neurotoxic effects of increased porphyrin precursors, although the underlying pathophysiology of porphyric neuropathy remains unclear. To further investigate the neurotoxic effect of porphyrins, excitability measurements (stimulus-response, threshold electrotonus, current–threshold relationship and recovery cycle) of peripheral motor axons were undertaken in 20 AIP subjects combined with the results of genetic screening, biochemical and conventional nerve conduction studies. Compared with controls, excitability measurements from five latent AIP patients were normal, while 13 patients who experienced acute porphyric episodes without clinical neuropathy (AIPWN) showed clear differences in their responses to hyperpolarizing currents (e.g. reduced hyperpolarizing I/V slope, P <>
Acute intermittent porphyria (AIP) is a rare metabolic disorder characterized by mutations of the porphobilinogen deaminase gene. Clinical manifestations of AIP are caused by the neurotoxic effects of increased porphyrin precursors, although the underlying pathophysiology of porphyric neuropathy remains unclear. To further investigate the neurotoxic effect of porphyrins, excitability measurements (stimulus-response, threshold electrotonus, current–threshold relationship and recovery cycle) of peripheral motor axons were undertaken in 20 AIP subjects combined with the results of genetic screening, biochemical and conventional nerve conduction studies. Compared with controls, excitability measurements from five latent AIP patients were normal, while 13 patients who experienced acute porphyric episodes without clinical neuropathy (AIPWN) showed clear differences in their responses to hyperpolarizing currents (e.g. reduced hyperpolarizing I/V slope, P <>
Key Words: porphyria; haem; nerve excitability; inward rectification (IH); ischaemia
Abbreviations: AIPWN, acute intermittent porphyria without neuropathy; AIPN, acute intermittent prophyric neuropathy; ALA, -aminolevulanic acid; ATP, adenosine triphosphate; APB, abductor pollicis brevis; CMAP, compound muscle action potential; Cr, creatinine; GBS, Guillain Barré syndrome; GH, inward rectifying conductance; HMBS, hydroxymethylbilane synthase gene; IH, hyperpolarizing activated conductance/inward rectification; PBGD, porphobilinogen deaminase; PN, porphyric neuropathy; TA, tibialis anterior; TE, threshold electrotonus
Received November 26, 2007. Revised May 8, 2008. Accepted June 20, 2008.
