TY - JOUR
T1 - McLeod neuroacanthocytosis
T2 - Genotype and phenotype
AU - Danek, Adrian
AU - Rubio, Justin P.
AU - Rampoldi, Luca
AU - Ho, Mengfatt
AU - Dobson-Stone, Carol
AU - Tison, François
AU - Symmans, William A.
AU - Oechsner, Matthias
AU - Kalckreuth, Wolfgang
AU - Watt, Julie M.
AU - Corbett, Alastair J.
AU - Hamdalla, Hisham H M
AU - Marshall, Andrew G.
AU - Sutton, Ian
AU - Dotti, Maria Teresa
AU - Malandrini, Alessandro
AU - Walker, Ruth H.
AU - Daniels, Geoff
AU - Monaco, Anthony P.
PY - 2001
Y1 - 2001
N2 - McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea-acanthocytosis suggests that the corresponding proteins - XK, huntingtin, and chorein - might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia.
AB - McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea-acanthocytosis suggests that the corresponding proteins - XK, huntingtin, and chorein - might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia.
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U2 - 10.1002/ana.10035
DO - 10.1002/ana.10035
M3 - Article
C2 - 11761473
AN - SCOPUS:0035202829
VL - 50
SP - 755
EP - 764
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 6
ER -