Cerebral Metabolic Alterations in McLeod Syndrome

The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with central nervous system manifestations resembling Huntington's disease. We examined 5 McLeod patients and 5 asymptomatic heterozygous females with fast multiple spin-echo spectroscopic imaging. Three patients with pronounced psychiatric or cognitive manifestations had pathological N-acetyl aspartate/(creatine + choline) ratios in frontal, temporal, and insular areas, with an individual pattern. Two patients with a severe choreatic movement disorder had unilateral thalamic alterations. One patient with moderate movement disorder and personality disorder had bilateral occipital alterations. One female heterozygote had unilateral insular metabolic alterations, possibly indicating subclinical cerebral involvement. Although the prominent psychiatric and cognitive manifestations in McLeod patients suggest significant and widespread cortical abnormalities, previous neuroradiological and histopathological data had not revealed definite extrastriatal pathology. Our findings demonstrating metabolic abnormalities in different brain regions of McLeod patients might either reflect neuronal dysfunction due to impaired basal ganglia-thalamo-cortical circuits or subtle structural alterations in the particular cerebral areas.