Disease 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 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. Diagnosis and testing 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. Management 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. | | Genetic counseling 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. |