Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

doi:10.7916/tohm.v0.708

Review

. 2019 Oct 10:9.

doi: 10.7916/tohm.v0.708. eCollection 2019.

Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

Martin Paucar^{1

2}, Alexander M R Taylor³, Marios Hadjivassiliou⁴, Brent L Fogel⁵, Per Svenningsson^{1

2}

Affiliations

¹ Department of Neurology, Karolinska University Hospital, Stockholm, SE.
² Department of Clinical Neuroscience, Karolinska Institute, Stockholm, SE.
³ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
⁴ Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
⁵ Department of Neurology, UCLA Program in Neurogenetics, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA, USA.

PMID: 31656689
PMCID: PMC6790008
DOI: 10.7916/tohm.v0.708

Review

Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

Martin Paucar et al. Tremor Other Hyperkinet Mov (N Y). 2019.

. 2019 Oct 10:9.

doi: 10.7916/tohm.v0.708. eCollection 2019.

Authors

Martin Paucar^{1

2}, Alexander M R Taylor³, Marios Hadjivassiliou⁴, Brent L Fogel⁵, Per Svenningsson^{1

2}

Affiliations

¹ Department of Neurology, Karolinska University Hospital, Stockholm, SE.
² Department of Clinical Neuroscience, Karolinska Institute, Stockholm, SE.
³ Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
⁴ Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
⁵ Department of Neurology, UCLA Program in Neurogenetics, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA, USA.

PMID: 31656689
PMCID: PMC6790008
DOI: 10.7916/tohm.v0.708

Abstract

Background: Ataxias represent a challenging group of disorders due to significant clinical overlap. Here, we present a patient with early-onset progressive ataxia, polyneuropathy and discuss how elevation of alpha fetoprotein (AFP) narrows the differential diagnosis.

Case report: Ataxia, polyneuropathy, and mild elevation of AFP are features compatible with ataxia with oculomotor apraxia type 2 (AOA2) but also with ataxia with oculomotor apraxia type 4 (AOA4). A genetic analysis demonstrated biallelic mutations in senataxin (SETX), confirming the diagnosis of AOA2.

Discussion: Mild elevation of AFP is found in patients with AOA2 and AOA4, and higher levels are commonly seen in ataxia-telangiectasia. AFP is a useful diagnostic tool but not a biomarker for disease progression in AOA2.

Keywords: Ataxia; alpha-fetoprotein; cerebellar atrophy; polyneuropathy; senataxin.

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Conflict of interest statement

Funding: Dr M Paucar’s and P. Svenningsson’s research is supported by Region Stockholm. Conflicts of Interest: The authors report no conflicts of interest. Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent. All patients who appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided.

Figures

**Figure 1**
**Neuroimaging in AOA2.** Midsagittal T1-weigthed brain MRI of the patient at age 27 showing moderate cerebellar atrophy and enlarged interfolial spaces.

See this image and copyright information in PMC

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References

1. Nicolaou P, Georghiou A, Votsi C, Middleton LT, Zamba-Papanicolaou E, Christodoulou K. A novel c.5308_5311delGAGA mutation in senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia. BMC Med Genet 2008;9:28. doi: 10.1186/1471-2350-9-28 - DOI - PMC - PubMed
1. Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, et al. . Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain 2009;132:2688–2698. doi: 10.1093/brain/awp211. Epub 2009 Aug 20 - DOI - PubMed
1. Moreira MC, Koenig M. Ataxia with oculomotor apraxia type 2. 2004 Nov 15 [updated 12 July 2018]. In: Adam MP, Ardinger HH, Pagon RA, et al.., editors.. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993–2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1154/ [cited 12 September 2019].
1. Duquette A, Roddier K, McNabb-Baltar J, Gosselin I, St-Denis A, Dicaire MJ, et al. . Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann Neurol 2005;57:408–414. doi: 10.1002/ana.20408 - DOI - PubMed
1. Moreira MC, Klur S, Watanabe M, Németh AH, Le Ber I, Moniz JC, et al. . Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 2004;36:225–227. doi: 10.1038/ng1303 - DOI - PubMed

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[1] Nicolaou P, Georghiou A, Votsi C, Middleton LT, Zamba-Papanicolaou E, Christodoulou K. A novel c.5308_5311delGAGA mutation in senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia. BMC Med Genet 2008;9:28. doi: 10.1186/1471-2350-9-28 - DOI - PMC - PubMed

[2] Nicolaou P, Georghiou A, Votsi C, Middleton LT, Zamba-Papanicolaou E, Christodoulou K. A novel c.5308_5311delGAGA mutation in senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia. BMC Med Genet 2008;9:28. doi: 10.1186/1471-2350-9-28 - DOI - PMC - PubMed

[3] Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, et al. . Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain 2009;132:2688–2698. doi: 10.1093/brain/awp211. Epub 2009 Aug 20 - DOI - PubMed

[4] Anheim M, Monga B, Fleury M, Charles P, Barbot C, Salih M, et al. . Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients. Brain 2009;132:2688–2698. doi: 10.1093/brain/awp211. Epub 2009 Aug 20 - DOI - PubMed

[5] Moreira MC, Koenig M. Ataxia with oculomotor apraxia type 2. 2004 Nov 15 [updated 12 July 2018]. In: Adam MP, Ardinger HH, Pagon RA, et al.., editors.. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993–2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1154/ [cited 12 September 2019].

[6] Moreira MC, Koenig M. Ataxia with oculomotor apraxia type 2. 2004 Nov 15 [updated 12 July 2018]. In: Adam MP, Ardinger HH, Pagon RA, et al.., editors.. GeneReviews® [Internet]. Seattle, WA: University of Washington; 1993–2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1154/ [cited 12 September 2019].

[7] Duquette A, Roddier K, McNabb-Baltar J, Gosselin I, St-Denis A, Dicaire MJ, et al. . Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann Neurol 2005;57:408–414. doi: 10.1002/ana.20408 - DOI - PubMed

[8] Duquette A, Roddier K, McNabb-Baltar J, Gosselin I, St-Denis A, Dicaire MJ, et al. . Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann Neurol 2005;57:408–414. doi: 10.1002/ana.20408 - DOI - PubMed

[9] Moreira MC, Klur S, Watanabe M, Németh AH, Le Ber I, Moniz JC, et al. . Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 2004;36:225–227. doi: 10.1038/ng1303 - DOI - PubMed

[10] Moreira MC, Klur S, Watanabe M, Németh AH, Le Ber I, Moniz JC, et al. . Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet 2004;36:225–227. doi: 10.1038/ng1303 - DOI - PubMed

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Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

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Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

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Abstract

Conflict of interest statement

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