Neuroacanthocytosis Treatment & Management

  • Author: Paula K Rauschkolb, DO; Chief Editor: Selim R Benbadis, MD   more...
 
Updated: Jan 20, 2010
 

Medical Care

The betalipoprotein disorders of abetalipoproteinemia and the hypobetalipoproteinemias cause a malabsorption of vitamins, especially vitamin E and also vitamins A and K. Treating the patient with high doses of these vitamins, especially vitamin E, ameliorates, but does not completely cure, these diseases.

For the choreiform/parkinsonian group, no specific treatment exists for the primary diseases. No attempts have yet been made to systematically collect observations regarding response to drugs. For choreiform and choreoathetoid movements (hyperkinesias), antipsychotics, such as haloperidol (Haldol), are still helpful. Second-generation antipsychotics may also be used as well as other medications such as tetrabenazine and tiapride.

Parkinsonian symptoms may respond to dopaminergic agents such as carbidopa-levodopa, ropinirole, and pramipexole. However, such agents tend to worsen chorea and could not be used unless a given patient had predominantly parkinsonian features (such as may occur in PKAN). Tremor may respond nonspecifically to either cholinergic agents such as benztropine (Cogentin) or trihexyphenidyl (Artane) or to medications used for essential tremor such as beta-blockers or primidone. One can consider botulinum toxin injection in treating both dystonias, choreoathetoid movements, and tremor. Some dyskinesias may respond to carbamazepine.[40]

For possible epileptic seizures, carbamazepine, oxcarbamazepine, and gabapentin are reasonable options.

The treatment is not based on a fundamental understanding of the diseases, but treatment that may work to suppress the symptoms without undue side effects is tried.

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Surgical Care

Deep brain stimulation was used to help two French patients with neuroacanthocytosis. One of them had a specific diagnosis of choreoacanthocytosis with an intronic mutation in the CHaC gene. The other had a diagnosis of McLeod syndrome (MLS) with weak Kell antigen expression and a mutation in the KX gene. Both had an extremely severe movement disorder with a combination of chorea and dystonia. One patient also had severe dysarthria, involuntary belching, and involuntary tongue biting. The other had hypotonia, postural instability, and cognitive deterioration. Both patients received bilateral globus pallidus stimulators. After extensive adjustment, blinded evaluation of "before" and "after" video by two independent movement disorder specialists showed significant improvement in each patient's chorea. The first patient also had an improvement in belching. However, the other aspects of their problems were not significantly improved.[41]

An earlier study of a single patient by a different group failed to show improvement in a patient with choreoacanthocytosis.[42] However, this was completed 6 years previously and technical knowledge of the details of positioning and regulating the stimulators has improved. The adjustments made in the two partially successful cases were very delicate, and small changes in stimulation parameters made major differences. Although these results are preliminary, they should be regarded as promising for future developments.

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Consultations

  • Psychiatrist: Psychiatric evaluation is indicated to diagnose and treat depression and/or other psychiatric disorders.
  • Consultations with rehabilitation specialists such as physiatrists, physical therapists, speech therapists, and occupational therapists are usually valuable.[43]
  • Nutritionist
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Diet

  • Maintain a balanced diet.
  • Consultation with a nutritionist may be appropriate.
  • In advanced cases, a soft diet and/or a GI feeding tube may become necessary.
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Activity

  • Typically, no restriction in activity is required until more advanced stages of the disease.
  • Fall and balance precautions should be observed.
  • In patients with advanced disease, walkers and/or wheelchairs may be appropriate.
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Contributor Information and Disclosures
Author

Paula K Rauschkolb, DO  Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center

Paula K Rauschkolb, DO is a member of the following medical societies: American Academy of Neurology and American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

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, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Roberta J Seidman, MD  Associate Professor of Clinical Pathology, Stony Brook University; Director of Neuropathology, Department of Pathology, Stony Brook University Medical Center

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), and Suffolk County Society of Pathologists

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Nestor Galvez-Jimenez, MD, MSc, MHA  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, and Movement Disorders Society

Disclosure: Nothing to disclose.

Chief Editor

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

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, and American Medical Association

Disclosure: UCB Pharma Honoraria Speaking, consulting; Lundbeck Honoraria Speaking, consulting; Cyberonics Honoraria Speaking, consulting; Glaxo Smith Kline Honoraria Speaking, consulting; Ortho McNeil Honoraria Speaking, consulting; Pfizer Honoraria Speaking, consulting; Sleepmed/DigiTrace Speaking, consulting

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Table 1. Most Common Neuroacanthocytosis Syndromes
OMIM#NameModeLocusOnset ageDescriptionPathology
#200150ChAc or Levine-Critchley syndrome[6, 7, 8, 13] Autosomal recessiveVPS13A (chorein); 9q21[13] 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.[6, 7, 8] Atrophy of the caudate, putamen, globus pallidus, and substantia nigra
+314850MLS[14] X-linkedKell blood group protein; Xp21Adult 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
#606438HDL2[15, 16] Autosomal dominantJPH3; 16q24.3Onset 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
#234200PKAN or PANK2 deficiency (previously termed Hallervorden-Spatz disease)[17] Autosomal recessivePANK2; 20p13Childhood onset (by 4-6 y); adult onset subtypes existFeatures 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
#200100Abeta-lipoprotein-emia[9, 10, 11, 12] Autosomal recessiveMTP; 4q22- q24Infancy / childhoodFeatures 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
+107730FHBL1[24, 25, 26, 27, 28] Autosomal recessiveAPOB; 2p24Infancy / childhoodFeatures 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.
%605019FHBL2[29, 30] Possibly autosomal recessive3p22-p21.2 for some, for others linkage not knownInfancy / childhoodFeatures are same as for FHBL1.Same as FHBL1
Table 2. Extremely Rare or Uncertain Causes of Neuroacanthocytosis
OMIMNameModeLocusDescription
#540000Mitochondrial encephalopathy, lactic acidosis, and stroke (MELAS) with acanthocytosis[31] Mitochondrial for MELAS but this case is not provenMitochondrial genome for MELAS but this case is not provenThis 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/AFamilial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy (FAPED)[32] 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.
#246700Anderson disease, now part of chylomicron retention disease (CMRD)Autosomal recessiveSar1B gene, 5q31.1[33] 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[34] and reference to same chapter[35] .
+278000 or 278100Atypical Wolman disease[36] 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)[36] . 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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