Abstract
Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome which have a Huntington´s disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's disease-like 2, autosomal recessive pantothenate kinase-associated neurodegeneration and several inherited disorders of lipoprotein metabolism, namely abetalipoproteinemia (Bassen-Kornzweig syndrome) and hypobetalipoproteinemia leading to vitamin E malabsorption. The latter disorders are characterized by a peripheral neuropathy and sensory ataxia due to dorsal column degeneration, but movement disorders and cognitive impairment are not present. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway. Laboratory tests include blood smears to detect acanthocytosis and determination of serum creatine kinase. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent in McLeod syndrome. Western blot for chorein demonstrates absence of this protein in red blood cells of chorea-acanthocytosis patients. Specific genetic testing is possible in all NA syndromes. Differential diagnoses include Huntington disease and other causes of progressive hyperkinetic movement disorders. There are no curative therapies for NA syndromes. Regular cardiologic studies and avoidance of transfusion complications are mandatory in McLeod syndrome. The hyperkinetic movement disorder may be treated as in Huntington disease. Other symptoms including psychiatric manifestations should be managed in a symptom-oriented manner. NA syndromes have a relentlessly progressive course usually over two to three decades.
Highlights
Neuroacanthocytosis (NA) syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia
Definition Neuroacanthocytosis (NA) refers to a heterogeneous group of syndromes in which nervous system abnormalities coincide with red blood cell acanthocytosis, i.e. deformed erythrocytes with spike-like protrusions (Figure 1) [1]
The so-called “core” NA syndromes characterized by degeneration of the basal ganglia, movement disorders, cognitive impairment and psychiatric features, and second, conditions with alteration
Summary
MELAS, mitochondrial encephalopathy with lactic acidosis and stroke-like episodes. Acanthocytosis in systemic diseases where neurological findings may be present Severe malnutrition (e.g. anorexia nervosa). Clinical Characteristics The core NA syndromes ChAc and MLS have a Huntington disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, representing phenocopies of HD. Both disorders have an adult onset and a slow progression. Chorea-Acanthocytosis ChAc is a progressive autosomal recessive neurodegenerative disorder with onset of neurological symptoms usually in the twenties, representing a late onset for an autosomal recessive disorder (Table 2) [1]. Often the initial presentation may be subtle cognitive or psychiatric symptoms, and in retrospect patients may have developed related psychiatric complaints several years before the neurological manifestations.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call