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X‐linked adrenomyeloneuropathy due to a novel missense mutation in the ABCD1 start codon presenting as demyelinating neuropathy
Author(s) -
Engelen Marc,
van der Kooi Anneke J.,
Kemp Stephan,
Wanders Ronald J. A.,
Sistermans Erik A.,
Waterham Hans R.,
Koelman Johannes T. M.,
van Geel Björn M.,
de Visser Marianne
Publication year - 2011
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1529-8027.2011.00367.x
Subject(s) - missense mutation , adrenoleukodystrophy , medical genetics , neurology , medicine , family medicine , genetics , mutation , biology , psychiatry , peroxisome , gene , receptor
Dear Editor, X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene which encodes the adrenoleukodystrophy protein (ALDP), a peroxisomal transmembrane protein (Mosser et al., 1993; Moser et al., 2001). Several often overlapping phenotypes can be distinguished. Approximately, half of all patients develop adrenomyeloneuropathy (AMN), characterized by slowly progressive spastic paraparesis, peripheral neuropathy, sphincter dysfunction, and adrenocortical insufficiency (Moser et al., 2001). We present a patient with an unusual neuropathy who was shown to have X-ALD caused by a mutation in the ABCD1 gene. A 27-year-old man presented with exercise-related weakness and fatigue in the legs which progressed slowly over the last 2 years. Three years prior to presentation he shortly used testosterone replacement therapy for decreased libido. Family history was negative for neuromuscular and endocrinological disorders. Physical examination revealed slight generalized wasting and weakness of the legs and decreased sensation for light touch at the dorsum of both feet with decreased position sense of the toes. Pes cavus was not present. Deep tendon reflexes were normal, and plantar reflexes were flexor. Electrophysiologic findings were compatible with a mild, symmetric demyelinating neuropathy confined to the lower limbs (Table 1). Serum creatine kinase activity was elevated (270 U/l, normal <193 U/l). Normal or negative results were obtained for thyroid stimulating hormone, sodium and potassium, and vasculitis parameters (Anti-neutrophil cytoplasmic antibody, antinuclear antibody and complement levels). Cerebrospinal fluid examination showed elevated protein (0.66 g/l, upper limit of normal 0.49). DNA analysis revealed no mutations in the PMP22 gene. Refsum’s