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 disorder, (2) cognitive impairment, and (3) psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and clinically relevant muscle weakness or atrophy. The hematologic manifestations are red blood cell acanthocytosis, compensated hemolysis, and the McLeod blood group phenotype resulting from absent expression of the Kx erythrocyte antigen and reduced expression of the Kell blood group antigens. The Kell blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in newborns of Kell-negative mothers. Heterozygous females have mosaicism for the Kell system blood group antigens and RBC acanthocytosis but lack CNS and neuromuscular manifestations.

The diagnosis of MLS is based on clinical and hematologic findings. XK is the only gene currently known to be associated with McLeod neuroacanthocytosis syndrome. Molecular genetic testing is available on a research basis only.

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

McLeod neuroacanthocytosis syndrome is inherited in an X-linked manner. If the mother of an affected male is a carrier, the chance of transmitting MLS in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and will usually not be affected. Affected males pass the disease-causing mutation to all of their daughters and none of their sons. No laboratories offering molecular genetic testing for prenatal diagnosis of MLS are listed in the GeneTests Laboratory Directory; however, prenatal testing may be available through laboratories offering custom prenatal testing.