Mcleod syndrome: A novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings

Abstract

The McLeod syndrome is an X-linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2-fluoro-2-deoxy-glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X-linked trait should be examined for acanthocytosis and Kell/Kx blood group serology.

Neuroacanthocytosis: new developments in a neglected group of dementing disorders

“…Most disease-causing XK mutations comprise deletions, nonsense mutations or splice site mutations predicting an absent or truncated XK protein devoid of the Kell protein binding site. No clear phenotype-genotype correlation was observed [10,47,48]. One XK missense mutation was associated with a prototypic neuroacanthocytosis phenotype [48].…”

“…Onset ranges between 18 years and 61 years, with a mean of about 35 years [47,48,[65][66][67]. Rarely, manifesting female heterozygous mutation carriers have been identified [67,68].…”

Cardiac abnormalities in McLeod syndrome

“…Six patients (IV-4, IV-5, IV-6, IV-7, IV-13, V-3) carried the Q299X nonsense mutation in the XK gene responsible for the McLeod syndrome [2]. One patient carried the E327 K missense mutation (II-2) [4].…”

“…CNS manifestations resemble Huntington's disease, and comprise choreatic movement disorder, psychiatric symptoms, subcortical cognitive decline, and generalized epileptic seizures [2,3]. About half of the McLeod patients have additional neuromuscular symptoms as well as electrocardio-or echocardiographic abnormalities [3].…”

“…The McLeod neuroacanthocytosis syndrome is an Xlinked multi-system disorder with hematological, cardiac, neuromuscular, and central nervous system (CNS) involvement [1][2][3]. CNS manifestations resemble Huntington's disease, and comprise choreatic movement disorder, psychiatric symptoms, subcortical cognitive decline, and generalized epileptic seizures [2,3].…”