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  • Updated 12.04.2020
  • Released 05.13.1994
  • Expires For CME 12.04.2023

Neuroacanthocytosis

Introduction

Overview

Neuroacanthocytosis is a neurologic syndrome characterized by a broad spectrum of movement disorders that often share acanthocytes on the blood smear. In addition to a variety of hyperkinetic and hypokinetic movement disorders, behavioral and cognitive disturbances are common features. An autosomal recessive disorder, chorea-acanthocytosis overlaps clinically with McLeod syndrome, which is inherited as an X-linked disorder. Neuroacanthocytosis must be considered in the differential diagnosis of patients presenting with movement disorders and behavioral/cognitive findings. Treatments, including deep brain stimulation, are met with various levels of success.

Key points

• Chorea-acanthocytosis is an autosomal recessive disorder due to mutations in the VPS13A gene (chromosome 9q21), and is among the disorders known to cause neuroacanthocytosis.

• Neuroacanthocytosis should be considered in the differential diagnosis of patients with neuropsychiatric symptoms and chorea or in adult onset tourettism.

• A tongue-protrusion “feeding dystonia” is highly suggestive of neuroacanthocytosis.

• A peripheral smear revealing 3% acanthocytes is considered positive, though in early cases, the smear may appear normal.

• A variety of other neurologic symptoms may accompany neuroacanthocytosis, including seizures, motor neuron disease, and dementia.

Historical note and terminology

Neuroacanthocytosis is an umbrella term for a rare multisystem neurodegenerative syndrome with several etiologies (114). Unifying these diverse conditions is the acanthocyte (acanth, “thorn,” Greek), an abnormal, contracted red blood cell, with several irregularly spaced thorny projections from the surface. Up to 3% acanthocytes in the peripheral blood smear may be considered normal; ranges beyond this are often associated with disease. Cases of neuroacanthocytosis typically are associated with striatal atrophy, subsequent movement disorders, behavioral changes, and a pattern of frontal subcortical dementia. Caudate atrophy, peripheral neuropathy, and myopathy are other core neuropathological features that arose in the literature early on (07). With the advent of gene testing, the classification of neuroacanthocytosis has allowed investigators to distinguish various etiologies.

Acanthocytosis was initially used as a term to describe abnormal red blood cells in the Bassen-Kornzweig syndrome of fat malabsorption (06). This blood abnormality in the setting of neurologic dysfunction was first reported in a New England family (75; 46). Levine described 21 members of a family with a dominantly inherited neurologic disorder and acanthocytes, though some were noted to have the histologically distinct Burr cells (echinocytes) as well, in the peripheral blood smear (46). Most symptomatic individuals had acanthocytes on their smear, as did 3 asymptotic relatives. In the following years, other symptoms were described among these individuals, including muscle weakness, leg cramps, lack of coordination, epilepsy, chorea, distal sensory deficits, dementia, and gait disorder (20).

Critchley reported a second family with chorea, self-mutilation, areflexia, dementia, and a characteristic eating dystonia: "when he ate his tongue would involuntarily push his food out onto the plate" (09). Affected individuals were found in 2 generations. The disease was known for some period as Levine-Critchley syndrome, but it is often now reported varyingly as amyotrophic chorea-acanthocytosis or, more commonly, neuroacanthocytosis, a term coined originally by Jankovic and colleagues to draw attention to the heterogeneous presentation with a variety of hyperkinetic movement disorders (chorea, dystonia, tics) and hypokinetic movement disorders (parkinsonism) in addition to other neurologic deficits and abnormal laboratory findings (34). Spitz and colleagues subsequently defined neuroacanthocytosis as a rare neurodegenerative disorder characterized by acanthocytes in the peripheral blood smear, motor neuron disease, and movement disorders; including such manifestations as chorea, tongue and lip biting, parkinsonism, orofacial dyskinesias, and vocal and facial tics (88).

Neuroacanthocytosis is currently classified as follows (95): (1) neuroacanthocytosis with normal serum lipoproteins, (2) neuroacanthocytosis with hypobetalipoproteinemia, (3) neuroacanthocytosis with abetalipoproteinemia, and (4) X-linked neuroacanthocytosis (McLeod syndrome). “Core neuroacanthocytosis syndromes” included in this spectrum are the autosomal-recessive chorea-acanthocytosis, the X-linked McLeod syndrome, Huntington disease-like 2, and pantothenate kinase-associated neurodegeneration (12).

Bassen Kornzweig disease, in which acanthocytes are present in concert with ataxia, retinitis pigmentosa, proprioceptive sensory loss, and areflexia, is included as a less common cause of neuroacanthocytosis. However, there is usually no deficiency of beta-lipoprotein in other etiologies. Other reported neurologic syndromes with associated acanthocytosis include neurodegeneration with brain iron accumulation, Huntington disease-like 2 (106), and 2 cases of mitochondrial encephalopathy.

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