Neuroacanthocytosis

Neuroacanthocytosis (NA) syndromes are a group of genetic diseases characterized by the association of red blood cell acanthocytosis (deformed erythrocytes with spike-like protrusions) and progressive degeneration of the basal ganglia.

Epidemiology

NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5/1,000,000 for each disorder.

Clinical description

NA syndromes include choreacanthocytosis, McLeod neuroacanthocytosis syndrome, pantothenate-kinase-associated neurodegeneration, and Huntington disease-like 2 (see these terms) which have a Huntington disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. Cardiomyopathy including arrhythmias may occur in McLeod syndrome.

Etiology

NA syndromes are caused by disease-specific genetic mutations. The mechanisms by which these mutations cause neurodegeneration are not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway.

Genetic counseling

Choreacanthocytosis follows an autosomal recessive pattern of inheritance, McLeod neuroacanthocytosis syndrome an X-linked pattern, and Huntington disease-like 2 an autosomal dominant pattern.