McLeod syndrome (MLS)

McLeod syndrome (MLS) is a recessive X-linked disease usually manifesting in middle age

• membrane transport protein Kx, a protein of vague function and wide tissue distribution, is a product of the XK gene in locus Xp21
  • also expressed on erythrocytes, the Kx protein carries the erythrocytic antigen Kx
  • absence of the Kx protein leads to decreased erythrocytic expression of the Kell system antigens
  • the MLS phenotype is derived from various forms of XK gene defects that result in the absence of XK protein, and is defined hematologically by the absence of Kx antigen, weakening of Kell system antigens, and red cell acanthocytosis
• characteristic features of MLS comprise
  • individuals with the McLeod phenotype usually develop late-onset neuromuscular abnormalities known as the McLeod syndrome (MLS)
  • development of choreatic dyskinesia, polyneuropathy, myopathy and cardiomyopathy
  • frequent cognitive and behavioural changes accompanied in some cases with parkinsonian syndrome, dysphagia, epileptic paroxysms or hepatosplenomegaly
• investigations
  • neuroimaging usually helps to detect basal ganglia atrophy
  • blood smears often show the presence of acanthocytes
  • increased creatine kinase (CK), often also elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamyl transferase (GMT)
• MLS takes a progressive course leaving practically no scope for causal treatment

Notes:

• MLS is an X-linked multi-system disorder caused by absence of XK alone, or when the disorder is caused by large deletions, it may be accompanied with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CYBB), retinitis pigmentosa (RPGR), and ornithine transcarbamylase deficiency (OTC)

Reference:

• (1) Allen FH et al. A new phenotype (McLeod) in the Kell blood-group system, Vox Sang 1961;6: 555–560.
• (2)Danek A et al. McLeod neuroacanthocytosis: genotype and phenotype. Ann Neurol 2001;50:755–764.
• (3) Peng J et al. Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases.Gene. 2007 May 1;392(1-2):142-50