McLeod neuroacanthocytosis: Genotype and phenotype

McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unkn own function. Originally defined as a peculiar Kell blood group variant, th e disease affects multiple organs, including the nervous system, but is cer tainly underdiagnosed. We analyzed the mutations and clinical findings of 2 2 affected men, aged 27 to 72 years. Fifteen different XK mutations were fo und, nine of which were novel, including the one of the eponymous case McLe od. Their common result is predicted absence or truncation of the XK protei n. All patients showed elevated levels of muscle creatine phosphokinase, bu t clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected i n 15 patients, as obvious from the occurrence of seizures, cognitive impair ment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in I asymptomatic young patient. Most features develop with age, mainly after th e fourth decade. The resemblance of McLeod syndrome with Huntington's disea se and with autosomal recessive chorea-acanthocytosis suggests that the cor responding proteins-XK, huntingtin, and chorein-might belong to a common pa thway, the dysfunction of which causes degeneration of the basal ganglia.