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A Twelve-Year Follow-Up Study on a Case of Early-Onset Parkinsonism Preceding Clinical Manifestation of Gaucher Disease

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JIMD Reports - Case and Research Reports, 2011/3

Part of the book series: JIMD Reports ((JIMD,volume 3))

Abstract

Mutations in the glucocerebrosidase gene (GBA1) cause Gaucher disease (GD) and are the most common genetic risk factor for the development of Parkinson’s disease (PD). Here, we present a 12-year follow-up study of a male with GD and PD (diagnosed 24years ago), which PD preceded the clinical manifestation of GD by 12years. The patient is a compound heterozygote for mutations c.115+1G>A and c.1226A>G (IVS2 + 1/N370S) in the GBA1 gene. Imiglucerase had a beneficial effect on GD, but not on PD. Treatment with L-dopa and other PD drugs showed temporary efficacy but 2years later significant wearing-off phenomenon and dyskinesias appeared. Unilateral pallidotomy was performed with transient benefit. Cognitive decline appeared later and developed in to akinetic mutism. A lumbar puncture was performed to characterize the biochemical profile of cerebrospinal fluid (CSF). Analyses of monoamine metabolites levels in the CSF, determined by reverse-phase high-performance liquid chromatography, revealed remarkably low levels of all studied monoamine metabolites (HVA, DOPAC, 5-HIAA, MHPG). These data indicate that PD associated with GBA1 mutations may not only affect dopaminergic neurons, but also noradrenergic and serotonergic neurons. Of note, normal levels of P-tau, total tau and β-amyloid (1–42) were detected on ELISA assay. Thus, the cognitive decline, akinetic mutism and moderate cortical atrophy found on the CT scan were not paralleled by any changes of dementia markers in CSF. This single case study extends the follow-up period and adds novel CSF information; however additional data on other patients with both PD and GD may help put our observations in its ultimate proper context.

Competing interests: None declared.

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Abbreviations

ADL:

Activities of daily living

CSF:

Cerebrospinal fluid

DBS:

Deep brain stimulation

ERT:

Enzyme replacement therapy

GBA:

Glucocerebrosidase

GD:

Gaucher disease

GD1:

Gaucher disease type 1

LSD:

Lysosomal storage disorder

PD:

Parkinson’s disease

P-tau:

Phosphorylated tau protein (181P)

RBD:

REM-sleep behavioral disorder

Tau:

Total tau protein

UPDRS:

Unified Parkinson’s disease rating scale

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Acknowledgments

This study was supported by The Swedish Research Council (PS) and Karolinska University Hospital (MM, MPA, PS). We thank the patient and his wife for participation in this study.

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Authors and Affiliations

  1. Hematology Center Karolinska, M54, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Maciej Machaczka

  2. Department of Neurology, Karolinska University Hospital Huddinge, 141 86, Stockholm, Sweden

    Martin Paucar Arce & Per Svenningsson

  3. Department of Hematology, Collegium Medicum of the Jagiellonian University, Krakow, Poland

    Malgorzata Rucinska, Wojciech Jurczak & Aleksander B. Skotnicki

  4. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Martin Paucar Arce & Per Svenningsson

  5. Department of Pharmacology and Physiology, Karolinska Institutet, Stockholm, Sweden

    Takashi Yoshitake & Jan Kehr

  6. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

    Jan-Erik Månsson

  7. Department of Metabolic Diseases, Endocrinology and Diabetology, The Children’s Memorial Health Institute, Warszawa, Poland

    Anna Tylki-Szymanska

Authors
  1. Maciej Machaczka
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  2. Martin Paucar Arce
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  3. Malgorzata Rucinska
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  4. Takashi Yoshitake
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  5. Jan Kehr
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  6. Wojciech Jurczak
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  7. Aleksander B. Skotnicki
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  8. Jan-Erik Månsson
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  9. Anna Tylki-Szymanska
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  10. Per Svenningsson
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Corresponding author

Correspondence to Maciej Machaczka .

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Editors and Affiliations

    Additional information

    Communicated by: Gregory M. Pastores.

    Appendices

    Synopsis

    The article reports the longest follow-up of Parkinson’s disease associated with Gaucher disease and provides the clinical and biochemical data on this association.

    Financial Disclosures

    MM: Advisor/honoraria/financial support to attend meetings from Genzyme Corporation, Actelion Pharmaceuticals, Shire HGT and BMS. MPA: none. MR: none. TY: none. YK: none. WJ: Advisor/honoraria/financial support to attend meetings from Novartis and Roche. ABS: Advisor/honoraria/financial support to attend meetings from BMS. JEM: none. ATS: Advisor/honoraria/financial support to attend meetings from Genzyme Corporation. PS: none.

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    © 2011 SSIEM and Springer-Verlag Berlin Heidelberg

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    Machaczka, M. et al. (2011). A Twelve-Year Follow-Up Study on a Case of Early-Onset Parkinsonism Preceding Clinical Manifestation of Gaucher Disease. In: JIMD Reports - Case and Research Reports, 2011/3. JIMD Reports, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_48

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    • DOI: https://doi.org/10.1007/8904_2011_48

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    • Publisher Name: Springer, Berlin, Heidelberg

    • Print ISBN: 978-3-642-24935-8

    • Online ISBN: 978-3-642-24936-5

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