McLeod phenotype without the McLeod syndrome

• Published in: Transfusion (Philadelphia, Pa.) Vol. 47; no. 2; pp. 299 - 305
• Main Authors: Walker, Ruth H., Danek, Adrian, Uttner, Ingo, Offner, Robert, Reid, Marion, Lee, Soohee
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.02.2007; Blackwell Publishing
• Subjects: Amino Acid Transport Systems, Neutral - genetics; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Chorea - genetics; Chorea - physiopathology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Variation; Genotype; Hematologic and hematopoietic diseases; Humans; Immunohematology; Immunophenotyping; Kell Blood-Group System - genetics; Male; Medical sciences; Middle Aged; Other diseases. Hematologic involvement in other diseases; Phenotype; Red blood cell immunology; Severity of Illness Index; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Sex linked character; Neuromuscular diseases; Nervous system diseases; Phenotype; Transfusion; MacLeod syndrome; Central nervous system disease; Hemopathy
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/j.1537-2995.2007.01106.x

BACKGROUND: McLeod neuroacanthocytosis syndrome is a late‐onset X‐linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype‐genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. STUDY DESIGN AND METHODS: Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption‐elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. RESULTS: Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. CONCLUSIONS: The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.