Summary
McLeod neuroacanthocytosis syndrome (MLS) is a multisystem disorder with central nervous system, neuromuscular, and hematologic manifestations in males. About 150 cases have been reported worldwide. The disease has a late-onset and slowly progressive course. Onset of neurological symptoms ranges between 20 and 60 years. The main clinical manifestations include a movement disorder, cognitive impairment and psychiatric symptoms. Each sign and symptom may develop in isolation or in variable combinations. Choreiform movements develop in up to 95% of patients over time. About 50% of individuals with MLS develop clinically relevant muscle weakness or atrophy during the disease course. Psychiatric abnormalities (personality disorder, anxiety, depression, obsessive-compulsive disorder, bipolar disorder, or schizoaffective disorder) and generalized seizures may affect 20-40% of patents. Red blood cell acanthocytosis is found in virtually all males with MLS. Hepatosplenomegaly occurs in about one third of males with MLS (all patients have elevated serum creatine phosphokinase concentrations, reaching values of up to 4000 U/L, and serum liver enzymes may also be elevated). Cardiac manifestations (dilated cardiomyopathy, atrial fibrillation, and tachyarrhythmia) may develop in up to 60% of patients over time. MLS is inherited in an X-linked manner. XK is the only gene currently associated with the disease, three XK missense mutations have been described. MLS features have been found in heterozygote females in isolated cases. The diagnosis of MLS is based on clinical and hematologic findings. It is indicated by elevated liver enzymes and creatine kinase, and can be confirmed by demonstration of the absence of Kx antigens and a reduction in kell antigens on erythrocytes. Molecular genetic testing is available on a research basis only. Differential diagnoses include Huntington disease, other neuroacanthocytosis syndromes (hypobetalipoproteinemia types 1 and 2, abetalipoproteinemia, chorea-acanthocytosis, HARP syndrome), Wilson disease, and Lesch-Nyhan syndrome (see these terms). Management requires treatment of the cardiac abnormalities, seizures and psychiatric disorders. Cardiac disease, in particular tachyarrhythmia, appears to be a major cause of premature death in MLS. Dopamine antagonists are used to ameliorate the choreatic movement disorder. Continuous multidisciplinary psychosocial support should be offered. *Author: Orphanet (January 2008)*.
