Benign X- Linked Myopathy With Acanthocytes (Mcleod Syndrome)

Abstract

Two healthy men with McLeod syndrome, a rare X-linked recessive phenotype characterized by acanthocytosis and weakened red blood cell antigenicity in the Kell blood group system, have been investigated. Both men showed raised blood creatine kinase levels, with myopathic EMG abnormalities. Biopsies of the quadriceps muscle showed the features of an active myopathy although there was no clinical evidence of muscular abnormality. The combination of the association of membrane abnormalities in red blood cells and a myopathy in both McLeod phenotype and Duchenne muscular dystrophy suggests that these syndromes may be due to related genetic abnormalities. The genetic locus for McLeod phenotype is situated near the end of the short arm of the X chromosome. The locus for Duchenne muscular dystrophy is unknown but it has been postulated that it is also situated on the short arm of the X chromosome at Xp 21. The occurrence of a subclinical X-linked myopathy with acanthocytosis (McLeod phenotype) thus raises the possibility of a new approach to genetic investigations in Duchenne muscular dystrophy, and in the related milder forms of this disease.

Report of the committee on the genetic constitution of the X and Y chromosomes

“…The lod score for linkage between CGD and XG for reported families is no longer significant for close linkage and two recombinants have been found (Densen et al 1981; Schuurman and Tippett unpublished observations). The high lod score for XK and XG (mainly from two large families) still requires explanation although a recombinant was recently reported (Swash et al 1983).…”

Cerebral Metabolic Alterations in McLeod Syndrome

“…Neuromuscular manifestations may be subclinical or mild, and include myopathy, cardiomyopathy and sensorimotor axonal neuropathy [4,5,6]. Central nervous system manifestations resemble Huntington’s disease and comprise a choreatic movement disorder, psychiatric symptoms, subcortical cognitive decline, and generalized epileptic seizures [1, 3, 4].…”

Immunochemical analysis of the Kx protein from human red cells of different Kell phenotypes using antibodies raised against synthetic peptides

“…A slow progression to cardiomyopathy, skeletal muscle wasting and neurological defects is also associated with the syndrome (Swash et al, 1983;Carter et al, 1990;Danek et al, 1990Danek et al, , 1994Witt et al, 1992;Redman & Marsh, 1993). Although McLeod erythrocytes also exhibit a marked decrease of Kell blood group antigens, it is the Kx protein which is critical for the red cell membrane structure, since individuals of the K 0 phenotype that lack Kell but not Kx proteins on red cells do not suffer from any syndrome (Redman et al, 1988).…”