From the Research
McLeod syndrome is a rare X-linked genetic disorder primarily affecting males, characterized by abnormalities in the Kx blood group antigen and reduced expression of Kell antigens on red blood cells, with a complex clinical presentation that includes neurological, hematological, and muscular symptoms, as described in the most recent study 1.
Clinical Presentation
The condition typically manifests in middle age with a combination of:
- Neurological symptoms, such as progressive chorea (involuntary movements), seizures, cognitive decline, and peripheral neuropathy
- Hematological symptoms, including acanthocytosis (spiky red blood cells) and compensated hemolysis
- Muscular symptoms, such as elevated serum creatinine kinase (CK) and mild chronic neurogenic atrophy without overt myopathic features
Diagnosis and Management
Diagnosis of McLeod syndrome has management implications, as patients are at risk of severe transfusion reactions and cardiac complications, and should be based on a combination of clinical evaluation, laboratory tests, and genetic analysis, as recommended in the study 1. Treatment focuses on symptom management, with neurological symptoms potentially treated with medications like tetrabenazine or antipsychotics for movement disorders, while cardiac issues require regular monitoring and standard heart failure treatments when indicated. Patients should undergo regular neurological and cardiac evaluations, including echocardiograms and electrocardiograms, to monitor the progression of the disease and adjust treatment accordingly.
Genetic Basis and Counseling
The condition results from mutations in the XK gene on the X chromosome, which encodes the XK protein that carries the Kx antigen and is associated with the Kell glycoprotein, as described in the study 2. Due to its X-linked inheritance pattern, genetic counseling is recommended for affected families, especially for female carriers planning pregnancies, to provide them with information about the risk of transmission and the availability of genetic testing.