Small nerve fiber involvement is frequent in X-linked adrenoleukodystrophy.
OBJECTIVE
To investigate the presence of small nerve fiber dysfunction in subjects with X-linked adrenoleukodystrophy.


METHODS
Cross-sectional study in which 11 Norwegian subjects (3 males, 8 females) with X-linked adrenoleukodystrophy, phenotypes ranging from asymptomatic to wheelchair-bound with adrenomyeloneuropathy, were investigated with neurophysiologic studies including EMG, nerve conduction velocities, quantitative sensory testing, tests of autonomic function, and skin biopsy for intraepidermal nerve fiber density measurements.


RESULTS
We found small nerve fiber dysfunction in 10 of 11 subjects, increasing with age and more pronounced in males. Low intraepidermal nerve fiber densities were found in 5 of 11 subjects, indicating a loss of thin unmyelinated nerve fibers peripherally. Five of 11 subjects showed small nerve fiber dysfunction despite normal nerve fiber densities, suggesting possible involvement of the spinothalamic tracts. Two subjects showed moderate abnormalities in autonomic function tests.


CONCLUSIONS
Evidence of small nerve fiber dysfunction was widespread in this cohort of subjects with X-linked adrenoleukodystrophy, with findings indicating loss of peripheral small nerve fibers and possibly also fibers of the spinothalamic tracts. The results support the theory of primary axonal degeneration in adrenomyeloneuropathy. Evidence of nervous system involvement was found in all heterozygotes, with severity increasing with age. Clinicians caring for these patients should be alert to signs of small nerve fiber involvement.
From the Department of Neurology (M.A.H., E.J., C.M.E.T., K.B.N.), Oslo University Hospital; University of Oslo (M.A.H., E.J., C.M.E.T.); Department of Neuroscience (K.B.N.), Norwegian University of Science and Technology, Trondheim; Department of Neurology (S.I.M.), University Hospital of Northern Norway; and Department of Clinical Medicine (S.I.M.), UiT The Arctic University of Norway.
Morten A
MA
Horn
Kristian B
KB
Nilsen
Ellen
E
Jørum
Svein I
SI
Mellgren
Chantal M E
CM
Tallaksen
D000326:Adrenoleukodystrophy / Q000150:complications* / Q000503:physiopathology*; D000367:Age Factors; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004817:Epidermis / Q000294:innervation; D004916:Erythromelalgia / Q000150:complications* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications / Q000503:physiopathology*; D009431:Neural Conduction; D012727:Sex Characteristics