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McLeod Neuroacanthocytosis Syndrome.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2004 Dec 3 [updated 2012 May 17].

Excerpt

CLINICAL CHARACTERISTICS:

McLeod neuroacanthocytosis syndrome (designated as MLS throughout this review) is a multisystem disorder with central nervous system (CNS), neuromuscular, and hematologic manifestations in males. CNS manifestations are a neurodegenerative basal ganglia disease including (1) movement disorders, (2) cognitive alterations, and (3) psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and muscle weakness or atrophy of different degrees. Hematologically, MLS is defined as a specific blood group phenotype (named after the first proband, Hugh McLeod) that results from absent expression of the Kx erythrocyte antigen and weakened expression of Kell blood group antigens. The hematologic manifestations are red blood cell acanthocytosis and compensated hemolysis. Allo-antibodies in the Kell and Kx blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in newborns of Kell-negative mothers. Females heterozygous for XK pathogenic variants have mosaicism for the Kell and Kx blood group antigens but usually lack CNS and neuromuscular manifestations; however, some heterozygous females may develop clinical manifestations including chorea or late-onset cognitive decline.

DIAGNOSIS/TESTING:

The diagnosis of MLS is based on findings on clinical examination, immunohematologic testing, and flow cytometry. XK is the only gene in which pathogenic variants are known to cause MLS. Contiguous gene deletions involving XK may also include CYBB (causing X-linked chronic granulomatous disease); DMD (Duchenne muscular dystrophy); and RPGR (X-linked retinitis pigmentosa).

MANAGEMENT:

Treatment of manifestations: Dopamine antagonists (e.g., tiapride, clozapine, quetiapine) and the dopamine depletory (tetrabenazine) may be used to ameliorate chorea; treatment of psychiatric problems, cardiac abnormalities, and seizures are based on the clinical findings; long-term and continuous multidisciplinary psychosocial support is needed for affected individuals and their families. Prevention of secondary complications: Kx-negative blood or banked autologous blood for transfusions when possible. Surveillance: Holter ECG and echocardiography every two to three years in those without known cardiac complications; consider placement of prophylactic cardiac pacemaker; monitor for seizures; monitor serum CK concentrations for evidence of rhabdomyolysis if excessive movement disorders are present or if neuroleptic medications are being used.

GENETIC COUNSELING:

MLS is inherited in an X-linked manner. If the mother of an affected male is a carrier, the chance of transmitting the XK pathogenic variant in each pregnancy is 50%. Males who inherit the variant will be affected; females who inherit the variant will be carriers and will usually not be affected. Affected males pass the pathogenic variant to all of their daughters and none of their sons. Prenatal testing for pregnancies at increased risk is possible through laboratories offering either testing for the gene of interest or custom testing.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

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