Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Neuroacanthocytosis Clinical Presentation

  • Author: Stephen A Berman, MD, PhD, MBA; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: Oct 13, 2014
 

History

See the list below:

  • Involuntary movements
    • Chorea and dystonia, features of hyperkinetic movement disorders, are more frequent than tics and parkinsonism. Several of these disorders may be present simultaneously.
    • Parkinsonism eventually may replace the hyperkinetic state.
    • Orolingual dystonia causes eating problems, dysarthria, and dysphagia (ie, the tongue involuntarily pushes food out of the mouth).
  • Personality changes occur, including impulsivity, antisocial personality, distractibility, anxiety, depression, apathy, loss of introspection, and compulsivity.[24, 25]
  • A peculiar gait is characterized by lurching with long strides and quick, involuntary knee flexion.
  • Seizures, generally tonic-clonic (ie, grand mal), occur in 30-40% of patients; they are infrequent and relatively easy to treat.
Next

Physical

See the list below:

  • The following signs are observed, in order of frequency: chorea, dystonia (including eating dystonia), other orolinguofacial dyskinesias (with lip biting[26] and dysarthria), vocal and/or motor tics, and parkinsonism.
  • Subcortical dementia with executive skill problems of the frontal lobe has been reported.
    • Executive skill problems include perseverative errors, excessive vulnerability to external intrusion, and inability to inhibit immediate and inappropriate responses to stimuli.
    • Visuopraxic disorders, anomia, and verbal as well as nonverbal memory retrieval problems may be noted.
  • Axonal neuropathy may present with the following signs:
    • Decreased or absent deep tendon reflexes
    • Muscle wasting (amyotrophy)
Previous
Next

Causes

Each major type of neuroacanthocytosis appears to have its own basic etiology, ie, the specific gene in which a mutation is present. The known mutant genes are listed with their respective diseases below.

  • The hereditary lipoprotein (typically betalipoprotein) disorders
    • Bassen-Kornsweig disease (abetalipoproteinemia) - Microsomal triglyceride transfer protein (MTP)[11, 12, 13, 14]
    • Familial hypobetalipoproteinemia (FHBL)
    • Other lipoprotein disorders of unknown etiology
  • Hereditary movement disorders (choreiform or Parkinsonlike)
    • Chorea-acanthocytosis (ChAc)[15] - Chorein (VPS13A)
    • McLeod syndrome (MLS)[16] - Kell blood group protein
    • Huntington disease–like2 (HDL2)[17, 18] - Junctophilin-3 (JPH3)
    • Pantothenate kinase–associated neurodegeneration (PKAN) - Pantothenatekinase 2 (PANK2)[19]
    • Other genetic and sporadic disorders - Genes not yet elucidated, or multigenetic, or due to sporadic conditions[21]
  • Although the ultimate basic etiology of the genetic conditions that cause most of the cases of acanthocytosis is known, it is generally not known how the gene defect produces the pathophysiological abnormalities.
  • The etiology is best understood for the betalipoprotein deficiencies. Lack of microsomal triglyceride transfer protein (MTP) or a direct mutation in the gene for betapolipoprotein leads to a decreased absorption of vitamin E as well as other vitamins and possibly other cofactors. This leads to damage to the dorsal root ganglia, spinocerebellar tracts, retina, and cerebellum. It also leads to a defect in the conformation and/or fluidity of the erythrocyte membrane. Band three of the membrane appears to be one of the components significantly involved.
  • For the other genetic disorders, the connections between the gene defects and the pathophysiological changes are not known. Again, changes in erythrocyte membrane conformation and/or fluidity (possibly via band three) may be involved in the changes underlying the acanthocytosis. Despite the enormous progress in understanding the molecular biology of these syndromes, there are still cases that do not fit the present understand precisely. Much work remains to be done.[20, 21]
  • To better understand the many different types of neuroacanthocytosis, the most common varieties have been organized into a table. The first column lists the Online Mendelian Inheritance in Man number (OMIM#). The Mendelian Inheritance in Man (MIM) catalog (not online) was developed by Dr. Victor McKusick and colleagues at Johns Hopkins University, and the OMIM is hosted by the US National Center for Biotechnology Information on what is essentially the same Web site as PubMed. Also provided in the table are the name, mode of inheritance, locus (including the chromosomal region and the names of the gene and protein if available), onset age, description of the condition, and the pathology.

Table 1. Most Common Neuroacanthocytosis Syndromes (Open Table in a new window)

OMIM#NameModeLocusOnset ageDescriptionPathology
#200150ChAc or Levine-Critchley syndrome[8, 9, 10, 15] Autosomal recessiveVPS13A (chorein); 9q21[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
+314850MLS[16] 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[17, 18] 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)[19] 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[11, 12, 13, 14] 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[27, 28, 29, 30, 31] 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[32, 33] Possibly autosomal recessive3p22-p21.2 for some, for others linkage not knownInfancy / childhoodFeatures are same as for FHBL1.Same as FHBL1

See the list below:

  • The diseases in the Table 2 are even rarer than those listed in the previous table. In some of these, the neuroacanthocytosis appears to represent an exception and possibly idiosyncratic reaction seen in some patients with concomitant diseases; however, the full range of acanthocytosis is not yet completely understood. What in current practice may appear to be an isolated idiosyncratic case may, in the future, stand as a part of a broader syndrome.

Table 2. Extremely Rare or Uncertain Causes of Neuroacanthocytosis (Open Table in a new window)

OMIMNameModeLocusDescription
#540000Mitochondrial encephalopathy, lactic acidosis, and stroke (MELAS) with acanthocytosis[34] 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)[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.
#246700Anderson disease, now part of chylomicron retention disease (CMRD)Autosomal recessiveSar1B 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 278100Atypical 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.

See the list below:

  • Various systemic diseases may also be accompanied by acanthocytosis and neurologic findings, especially in severely ill patients. These include various cancers, thyroid disorders, patients who have had a splenectomy, cirrhosis of the liver and hepatic encephalopathy, psoriasis, and an obscure condition called Eales disease in which an idiopathic inflammatory venous occlusion primarily affects the peripheral retina in adults. In these conditions, the presentation as neuroacanthocytosis may be a coincidence in which some type of neurologic insult, such as a stroke due to vasculitis, coincides with bone marrow failure in a severely ill individual; alternatively, a more fundamental connection may be present that is not currently understood.
Previous
 
 
Contributor Information and Disclosures
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.

Coauthor(s)

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.

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 College of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Additional Contributors

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, Suffolk County Society of Pathologists, New York Association of Neuropathologists (The Neuroplex), American Association of Neuropathologists

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.

References
  1. Bassen FA, Kornzweig AL. Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood. 1950 Apr. 5(4):381-87. [Medline].

  2. De Franceschi L, Bosman GJ, Mohandas N. Abnormal red cell features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes. Curr Opin Hematol. 2014 May. 21(3):201-9. [Medline].

  3. Siegl C, Hamminger P, Jank H, Ahting U, Bader B, Danek A, et al. Alterations of red cell membrane properties in neuroacanthocytosis. PLoS One. 2013. 8(10):e76715. [Medline]. [Full Text].

  4. Kartsounis LD, Hardie RJ. The pattern of cognitive impairments in neuroacanthocytosis. A frontosubcortical dementia. Arch Neurol. 1996 Jan. 53(1):77-80. [Medline].

  5. Medalia A, Merriam A, Sandberg M. Neuropsychological deficits in choreoacanthocytosis. Arch Neurol. 1989 May. 46(5):573-5. [Medline].

  6. Tiftikcioglu BI, Dericioglu N, Saygi S. Focal seizures originating from the left temporal lobe in a case with chorea-acanthocytosis. Clin EEG Neurosci. 2006 Jan. 37(1):46-9. [Medline].

  7. Rampoldi L, Danek A, Monaco AP. Clinical features and molecular bases of neuroacanthocytosis. J Mol Med. 2002 Aug. 80(8):475-91. [Medline].

  8. Levine IM, Estes JW, Looney JM. Hereditary neurological disease with acanthocytosis. A new syndrome. Arch Neurol. 1968 Oct. 19(4):403-9. [Medline].

  9. Estes JW, Morley TJ, Levine IM, Emerson CP. A new hereditary acanthocytosis syndrome. Am J Med. 1967 Jun. 42(6):868-81. [Medline].

  10. Critchley EM, Clark DB, Wikler A. Acanthocytosis and neurological disorder without betalipoproteinemia. Arch Neurol. 1968 Feb. 18(2):134-40. [Medline].

  11. Schwartz JF, Rowland LP, Eder H et al. Bassen-Kornzweig syndrome: deficiency of serum beta-lipoprotein. Arch. Neurol. 1963. 8:438-454.

  12. Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, et al. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature. 1993 Sep 2. 365(6441):65-9. [Medline].

  13. Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT, et al. Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. Hum Mol Genet. 1993 Dec. 2(12):2109-16. [Medline].

  14. Talmud PJ, Lloyd JK, Muller DP, Collins DR, Scott J, Humphries S. Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia. J Clin Invest. 1988 Nov. 82(5):1803-6. [Medline].

  15. Rampoldi L, Dobson-Stone C, Rubio JP, Danek A, Chalmers RM, Wood NW, et al. A conserved sorting-associated protein is mutant in chorea-acanthocytosis. Nat Genet. 2001 Jun. 28(2):119-20. [Medline].

  16. Walker RH, Jung HH, Tison F, Lee S, Danek A. Phenotypic variation among brothers with the McLeod neuroacanthocytosis syndrome. Movem Disord. 2007. 22(pt 2):244-8.

  17. Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, et al. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. Nat Genet. 2001 Dec. 29(4):377-8. [Medline].

  18. Margolis RL, O'Hearn E, Rosenblatt A. A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. Ann Neurol. 2001 Dec. 50(6):373-80. [Medline].

  19. Hayflick SJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KH, et al. Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. N Engl J Med. 2003 Jan 2. 348(1):33-40. [Medline].

  20. Spitz MC, Jankovic J, Killian JM. Familial tic disorder, parkinsonism, motor neuron disease, and acanthocytosis: a new syndrome. Neurology. 1985 Mar. 35(3):366-70. [Medline].

  21. Walker RH, Danek A, Dobson-Stone C, Guerrini R, Jung HH, Lafontaine AL, et al. Developments in neuroacanthocytosis: expanding the spectrum of choreatic syndromes. Mov Disord. 2006 Nov. 21(11):1794-805. [Medline].

  22. Lossos A, Dobson-Stone C, Monaco AP. Early clinical heterogeneity in choreoacanthocytosis. Arch Neurol. 2005 Apr. 62(4):611-4. [Medline].

  23. de Yebenes JG, Brin MF, Mena MA, et al. Neurochemical findings in neuroacanthocytosis. Mov Disord. 1988. 3(4):300-12. [Medline].

  24. Balhara YP, Varghese ST, Kayal M. Neuroacanthocytosis: presenting with depression. J Neuropsychiatry Clin Neurosci. 2006 Summer. 18(3):426. [Medline].

  25. Danek A, Bader B, Walker RH. Antisocial behaviour and neuroacanthocytosis. Int J Clin Pract. 2007 Aug. 61(8):1419; author reply 1419. [Medline].

  26. Gooneratne IK, Weeratunga PN, Gamage R. Teaching video neuroimages: orofacial dyskinesia and oral ulceration due to involuntary biting in neuroacanthocytosis. Neurology. 2014 Feb 25. 82(8):e70. [Medline].

  27. Aggerbeck LP, McMahon JP, Scanu AM. Hypobetalipoproteinemia: clinical and biochemical description of a new kindred with 'Friedreich's atazia'. Neurology. 1974 Nov. 24(11):1051-63. [Medline].

  28. Araki W, Hirose S, Mimori Y, Nakamura S, Kimura J, Ohno K, et al. Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex. J Intern Med. 1991 Feb. 229(2):197-9. [Medline].

  29. Bednarska-Makaruk M, Bisko M, Pulawska MF, Hoffman-Zacharska D, Rodo M, Roszczynko M, et al. Familial defective apolipoprotein B-100 in a group of hypercholesterolaemic patients in Poland. Identification of a new mutation Thr3492Ile in the apolipoprotein B gene. Eur J Hum Genet. 2001 Nov. 9(11):836-42. [Medline].

  30. Linton MF, Farese RV Jr, Young SG. Familial hypobetalipoproteinemia. J Lipid Res. 1993 Apr. 34(4):521-41. [Medline].

  31. Boren J, Ekstrom U, Agren B, Nilsson-Ehle P, Innerarity TL. The molecular mechanism for the genetic disorder familial defective apolipoprotein B100. J Biol Chem. 2001 Mar 23. 276(12):9214-8. [Medline].

  32. Pulai JI, Neuman RJ, Groenewegen AW, Wu J, Schonfeld G. Genetic heterogeneity in familial hypobetalipoproteinemia: linkage and non-linkage to the apoB gene in Caucasian families. Am J Med Genet. 1998 Feb 26. 76(1):79-86. [Medline].

  33. Yuan B, Neuman R, Duan SH, Weber JL, Kwok PY, Saccone NL, et al. Linkage of a gene for familial hypobetalipoproteinemia to chromosome 3p21.1-22. Am J Hum Genet. 2000 May. 66(5):1699-704. [Medline].

  34. Mukoyama M, Kazui H, Sunohara N, Yoshida M, Nonaka I, Satoyoshi E. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with acanthocytosis: a clinicopathological study of a unique case. J Neurol. 1986 Aug. 233(4):228-32. [Medline].

  35. Prof. Alexander Storch, MD, Dept. of Neurology,. Familial Acanthocytosis with Paroxysmal Exertion-induced Dyskinesias and epilepsy (FAPED). Dresden: Technical University of Dresden; [Full Text].

  36. Charcosset M, Sassolas A, Peretti N, Roy CC, Deslandres C, Sinnett D, et al. Anderson or chylomicron retention disease: molecular impact of five mutations in the SAR1B gene on the structure and the functionality of Sar1b protein. Mol Genet Metab. 2008 Jan. 93(1):74-84. [Medline].

  37. Al-Shali K, Hegele RA. Acanthocytes and disorders of lipoprotein. Danek A, ed. Neuroacanthocytosis syndromes. Dordrecht: Springer; 2004. 21-30.

  38. Danek A, Jung HH, Melone MA, Rampoldi L, Broccoli V, Walker RH. Neuroacanthocytosis: new developments in a neglected group of dementing disorders. J Neurol Sci. 2005 Mar 15. 229-230:171-86. [Medline].

  39. Eto Y, Kitagawa T. Wolman's disease with hypolipoproteinemia and acanthocytosis: clinical and biochemical observations. J Pediatr. 1970 Nov. 77(5):862-7. [Medline].

  40. Bohlega S, Riley W, Powe J. Neuroacanthocytosis and aprebetalipoproteinemia. Neurology. 1998. 50 (6):1912-1914. [Medline].

  41. Brooks DJ, Ibanez V, Playford ED, et al. Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis: a positron emission tomographic study. Ann Neurol. 1991 Aug. 30(2):166-71. [Medline].

  42. Dubinsky RM, Hallett M, Levey R, Di Chiro G. Regional brain glucose metabolism in neuroacanthocytosis. Neurology. 1989 Sep. 39(9):1253-5. [Medline].

  43. Tschopp L, Raina G, Salazar Z, Micheli F. Neuroacanthocytosis and carbamazepine responsive paroxysmal dyskinesias. Parkinsonism Relat Disord. 2008. 14(5):440-2. [Medline].

  44. Guehl D, Cuny E, Tison F, Benazzouz A, Bardinet E, Sibon Y. Deep brain pallidal stimulation for movement disorders in neuroacanthocytosis. Neurology. 2007 Jan 9. 68(2):160-1. [Medline].

  45. Wihl G, Volkmann J, Allert N, Lehrke R, Sturm V, Freund HJ. Deep brain stimulation of the internal pallidum did not improve chorea in a patient with neuro-acanthocytosis. Mov Disord. 2001 May. 16(3):572-5. [Medline].

  46. Mclntosh J. Speech/Occupational therapy for neuroacanthocytosis. Movem Disord. 2006. 20:1682.

  47. Lin FC, Wei LJ, Shih PY. Effect of levetiracetam on truncal tic in neuroacanthocytosis. Acta Neurol Taiwan. 2006 Mar. 15(1):38-42. [Medline].

  48. Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S, et al. Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nat Genet. 2003 May. 34(1):29-31. [Medline].

Previous
Next
 
Table 1. Most Common Neuroacanthocytosis Syndromes
OMIM#NameModeLocusOnset ageDescriptionPathology
#200150ChAc or Levine-Critchley syndrome[8, 9, 10, 15] Autosomal recessiveVPS13A (chorein); 9q21[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
+314850MLS[16] 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[17, 18] 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)[19] 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[11, 12, 13, 14] 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[27, 28, 29, 30, 31] 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[32, 33] 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[34] 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)[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.
#246700Anderson disease, now part of chylomicron retention disease (CMRD)Autosomal recessiveSar1B 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 278100Atypical 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.
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.