Laboratory Studies

See the list below:

Fresh blood smear for acanthocytes: Any level greater than 3% is abnormal; in neuroacanthocytosis, acanthocytes usually measure 10-30%. Liver disease, splenectomy, and hemolytic anemia must be excluded.
Elevated creatine kinase level
Serum lipoproteins: In addition to the abetalipoproteinemia and hypobetalipoproteinemia, a case report of a patient with aprebetalipoproteinemia has also been documented.^[40]All the forms probably have not yet been discovered.
Elevated liver enzyme levels
Specific genetic tests
- Bassen-Kornsweig disease (abetalipoproteinemia) -MTP gene
- FHBL1 -APOB gene
- ChAc - Chorein (VPS13A)
- MLS - Kell blood group protein (XK)
- HDL2 -JPH3 gene
- PKAN -PANK2 gene

Imaging Studies

See the list below:

Brain MRI - Caudate atrophy and increased signal in caudate and lentiform nuclei. In PKAN, a pallidal hypointensity with a central area of hyperintensity, named "eye of the tiger" sign, is observed. The hypointensity is due to iron deposition.
Brain CT scanning - Caudate atrophy and ventricular dilatation (especially in the frontal horns of the lateral ventricles)
Brain positron emission tomography - Hypometabolism in the neostriatum and the frontal cerebral cortical areas^{[41, 42]}
Brain single-photon emission computed tomography (SPECT) - Hypoperfusion in the neostriatum and frontal areas

Other Tests

See the list below:

Electromyography (EMG) and nerve conduction study (NCS) findings are consistent with chronic denervation and a primarily axonal peripheral neuropathy.

Treatment & Management

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Table 1. Most Common Neuroacanthocytosis Syndromes

OMIM#	Name	Mode	Gene, Locus, and Protein	Onset age	Description	Pathology
#200150	ChAc or Levine-Critchley syndrome^{[8, 9, 10, 15]}	Autosomal recessive	VPS13A 9q21 chorein^[15]	Adult onset; early to middle age (20-50 y)	Features include choreoathetosis, dystonia, parkinsonism, orofacial dyskinesias, seizures, and neuropathy. Whether the original index cases (ie, Levine, 1960 and 1968; Critchley, 1967 and 1970) were part of the Levine-Critchley syndrome as understood genetically today remain unknown.^{[8, 9, 10]}	Atrophy of the caudate, putamen, globus pallidus, and substantia nigra
+314850	MacLeod Syndrome or MLS^[16]	X-linked	Kell blood group gene, XK Xp21 locus XK protein	Adult onset middle to late age (40-70 y)	Features include choreoathetosis, dystonia, parkinsonism, seizures, neuropathy, myopathy, and cardiomyopathy.	Atrophy of the caudate, putamen, and globus pallidus; substantia nigra not involved
#606438	Huntington's Disease-Like 2, HDL2^{[17, 18]}	Autosomal dominant (CAG repeat expansion)	JPH3 16q24.3 Junctophilin-3	Onset earlier as repeat size increases (usually 30-40 y)	Features include choreoathetosis, dystonia, parkinsonism, hyperreflexia, dementia, and weight loss.	Atrophy of the caudate and putamen
#234200	PKAN or PANK2 deficiency (previously termed Hallervorden-Spatz disease)^[19]	Autosomal recessive	PANK2; 20p13	Childhood onset (by 4-6 y); adult onset subtypes exist	Features include choreoathetosis, dystonia, dysarthria, rigidity, spasticity, and dementia. PKAN also includes the HARP (hypoprebeta-lipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) subtype.	Iron deposition in the globus pallidus (causes "eye-of-the-tiger" sign on MRIs
#200100	Abeta-lipoprotein-emia^{[11, 12, 13, 14]}	Autosomal recessive	MTP; 4q22- q24	Infancy / childhood	Features include ataxia (sensory ataxia with some cerebellar features), visual loss, mental retardation / dementia, low vitamin E level, high cholesterol level, and abnormal lipoprotein electrophoresis.	Dorsal root ganglia, ascending sensory tracts, cuneate and gracile nuclei of cord, spinocere-bellar projections; possibly some direct cerebellar involvement; retinitis pigmentosa
+107730	FHBL1^{[27, 28, 29, 30, 31]}	Autosomal recessive	APOB; 2p24	Infancy / childhood	Features include ataxia (sensory ataxia with some cerebellar features), visual loss, and mental retardation / dementia.	Dorsal root ganglia, ascending sensory tracts, cuneate and gracile nuclei of cord, spinocere-bellar projections; possibly some direct cerebellar involvement; retinitis pigmentosa.
%605019	FHBL2^{[32, 33]}	Possibly autosomal recessive	3p22-p21.2 for some, for others linkage not known	Infancy / childhood	Features are same as for FHBL1.	Same as FHBL1

Table 2. Extremely Rare or Uncertain Causes of Neuroacanthocytosis

OMIM	Name	Mode	Locus	Description
#540000	Mitochondrial encephalopathy, lactic acidosis, and stroke (MELAS) with acanthocytosis^[34]	Mitochondrial for MELAS but this case is not proven	Mitochondrial genome for MELAS but this case is not proven	This is a single case. Typically, MELAS is an A3243G mutation. (Adenine is replaced by guanosine at position 3243 in the mitochondrial genome.) This single case report did not have mitochondrial genomic sequencing. Pathology reports showed abnormalities in Betz cells, brainstem neurons, and anterior horn cells. Muscle pathology results are compatible with MELAS.
N/A	Familial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy (FAPED)^[35]	Autosomal dominant (not certain; only one family)		This is characterized by intermittent attacks of cramps and involuntary movements; attacks are myoclonic and atonic epilepsy. It has been described in one family. MRI showed mild basal ganglia degeneration. Positron emission tomography scanning showed decreased glucose metabolism in the thalamus.
#246700	Anderson disease, now part of chylomicron retention disease (CMRD)	Autosomal recessive	Sar1B gene, 5q31.1^[36]	Severe intestinal fat malabsorption with diarrhea, steatorrhea, hypobetalipoproteinemia, low cholesterol, triglyceride and phospholipid levels, and failure to secrete chylomicrons after a fatty meal. Typically lacks acanthocytes, retinitis pigmentosa, and ataxia. Rare cases may be associated with acanthocytes and some neurologic problems and so may be considered neuroacanthocytosis. A single mention of features of neuroacanthocytosis is found in book chapter^[37]and reference to same chapter^[38].
+278000 or 278100	Atypical Wolman disease^[39]	Unknown (single case)	Unknown (single case)	In 1970, Eto and Kitagawa described a patient with lipid malabsorption, vomiting, growth failure, adrenal calcification, hypolipoproteinemia, and acanthocytosis and termed it Wolman disease (OMIM #278000)^[39]. The patient had hepatosplenomegaly, steatorrhea, abdominal distention, and adrenal calcification that appeared in the first weeks of life, as well as widespread accumulation of cholesterol esters and triglycerides in the internal organs. Typically, Wolman disease is not associated with acanthocytes or neurologic problems. This single case has now been given its own number (OMIM #278100). Whether this case is truly Wolman disease is uncertain.

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Author

Stephen A Berman, MD, PhD, MBA Professor of Neurology, University of Central Florida College of Medicine

Stephen A Berman, MD, PhD, MBA is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Additional Contributors

Roberta J Seidman, MD Associate Professor of Pathology, Director of Neuropathology, Department of Pathology, Renaissance School of Medicine at Stony Brook University, Stony Brook Medicine

Roberta J Seidman, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, New York Association of Neuropathologists (The Neuroplex)

Disclosure: Nothing to disclose.

Paula K Rauschkolb, DO Assistant Professor of Neurology and Medicine, Geisel School of Medicine at Dartmouth; Consulting Staff Physician, Department of Neurology, Department of Medicine, Section of Hematology/Oncology, Dartmouth-Hitchcock Medical Center

Paula K Rauschkolb, DO is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Society of Clinical Oncology, Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Maritza Arroyo-Muñiz, MD, to the development and writing of this article.

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