McLeod syndrome

Presentation

Patients usually begin to notice symptoms in their 30s and the course is usually slowly progressive. Common features include peripheral neuropathy, cardiomyopathy, and hemolytic anemia. Other features include limb chorea, facial tics, other oral movements (lip and tongue biting), seizures, a late-onset dementia, and behavioral changes.

Genetics

The McLeod phenotype is a recessive mutation of the Kell blood group system. The McLeod gene encodes the XK protein, which is located on the X chromosome, and has the structural characteristics of a membrane transport protein but an unknown function. Absence of the XK protein is an X-linked disease. Mutational variants result in McLeod syndrome either with or without neuroacanthocytosis: the gene on the X chromosome for McLeod syndrome is physically close to the gene for chronic granulomatous disease. As a result, an individual with one relatively small deletion may have both diseases.

The phenotype may be present without the syndrome presenting.

Diagnosis

Laboratory features

McLeod syndrome is one of only a few disorders in which acanthocytes may be found on the peripheral blood smear. Blood chemistry testing may show increased lactate dehydrogenase (LDH) indicative of hemolytic anemia or elevated creatine kinase when the patient is affected by myopathy (skeletal muscle damage).

Radiologic and pathologic features

MRI shows increased T2 signal in the lateral putamen with caudate atrophy and secondary lateral ventricular dilation. Necropsy shows loss of neurons and gliosis in the caudate and globus pallidus. Similar changes may also be seen in the thalamus, substantia nigra, and putamen. The cerebellum and cerebral cortex are generally spared.

Treatment

There is no cure for McLeod syndrome; the treatment is supportive depending on symptoms. Medication may assist with management of epilepsy, and cardiac and psychiatric features, although patients may respond poorly to treatment for chorea.

Prognosis

A typical patient with severe McLeod syndrome that begins in adulthood lives for an additional 5 to 10 years. Patients with cardiomyopathy have elevated risk for congestive heart failure and sudden cardiac death. The prognosis for a normal life span is often good in some patients with mild neurological or cardiac sequelae.

Epidemiology

McLeod syndrome is present in 0.5 to 1 per 100,000 of the population. McLeod males have variable acanthocytosis due to a defect in the inner leaflet bilayer of the red blood cell, as well as mild hemolysis. McLeod females have only occasional acanthocytes and very mild hemolysis; the lesser severity is thought to be due to X chromosome inactivation via the Lyon effect. Some individuals with McLeod phenotype develop myopathy, neuropathy, or psychiatric symptoms, producing a syndrome that may mimic chorea.

History

McLeod syndrome was discovered in 1961 and, similar to the Kell antigen system, was named after the first patient in which it was discovered; a Harvard dental student by the name of Hugh McLeod. McLeod's red blood cells demonstrated a peculiar appearance when viewed microscopically (acanthocytic (spiky)) and showed weak expression of Kell system antigens.

A pattern of pregnancy loss and infant deaths associated with the wives of King Henry VIII of England suggests he may have been Kell-positive and had McLeod syndrome given his eventual premature mental deterioration.

References

References

1. "McLeod neuroacanthocytosis syndrome".
2. (March 2009). "Identification and characterization of a novel XK splice site mutation in a patient with McLeod syndrome". Transfusion.
3. (February 1992). "Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21". Am. J. Hum. Genet..
4. (February 1975). "Chronic granulomatous disease and the Kell blood groups". Br. J. Haematol..
5. (February 2007). "McLeod phenotype without the McLeod syndrome". Transfusion.
6. (March 2005). "Neurological syndromes which can be mistaken for psychiatric conditions". J Neurol Neurosurg Psychiatry.
7. (2007). "Mc ''Leod'' myopathy revisited: More neurogenic and less benign". Brain.
8. (December 2001). "McLeod neuroacanthocytosis: genotype and phenotype". Ann. Neurol..
9. (June 1994). "Atypical McLeod syndrome manifested as X-linked chorea-acanthocytosis, neuromyopathy, and dilated cardiomyopathy: report of a family". J. Neurol. Sci..
10. (September 1961). "A new phenotype (McLeod) in the Kell blood-group system". Vox Sang..
11. "Discovery News: Henry VIII's eccentricities possibly explained".