Patient WA was a member of the New Zealand “S” family with an XK gene deletion, and was among the first patients with McLeod syndrome (MLS) comprehensively assessed by Laurence Marsh and collaborators in the 1970s. He displayed some hyperkinetic movements from his third decade of life and within 20 years developed a full picture of MLS: pathognomonic Kell phenotype, hepatosplenomegaly, cardiomyopathy, creatine kinase (CK) and liver enzyme elevation, muscle weakness and atrophy, neuropathy, dysarthria, dysphagia, chorea, and neuropsychiatric abnormalities. He died at the age of 50 years of unknown cause. The post mortem findings have not been fully reported up to now, although the autopsy study was the very first known of MLS. The neuropathological changes were largely limited to the striatum and consisted of bilateral neuronal loss and astrocytosis, more severe in the caudate nucleus than in the putamen. Only two other autopsy reports on MLS are available to date. These showed a similar picture to case WA and also resembled the findings in post mortem cases with a molecular diagnosis of chorea-acanthocytosis (ChAc).
A role for endothelins has been previously the subject of speculation as a potential mechanism for pathophysiology in MLS. However, this now seems implausible on the basis of recent expression studies of the endothelin-cleaving protein Kell and the McLeod protein XK in the brains of experimental animals and of humans. In brain only XK was found, whereas in red cell membranes and other peripheral tissues XK colocalises with Kell, to which it is covalently linked.
At present, study of the neuropathology of both conditions, MLS and ChAc, is still in its infancy. Increasing clinical recognition of neuroacanthocytosis syndromes and increasing availability of autopsy material will hopefully soon clarify some of the many open issues.
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Danek, A., Neumann, M., Brin, M.F., Symmans, W.A., Hays, A.P. (2008). Cerebral Involvement in McLeod Syndrome: The First Autopsy Revisited. In: Walker, R.H., Saiki, S., Danek, A. (eds) Neuroacanthocytosis Syndromes II. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71693-8_17
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