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S. Rajasankar, V. Venkateshgobi and S. Surendran
262
In one patient with PD, the rate of tremor increased progressively with
3-6 cycles per second by affecting distal part of the digits. Onset of the
tremor was in one limb for months then affects the other limb. When the
disease matures, tremor was observed in the tongue, eyelids and lips. Two
cases of PD patients showing symptoms are given in the Table 1.
8. CLINICAL SYMPTOMS OF GAUCHER DISEASE SUBTYPES
Patients with type 1 Gaucher disease show normal neurological
functions. Less than forty percentage children with the disease showed
growth retardation and delayed puberty. Splenomegaly, hepatomegaly,
pain in the pelvis and lower limbs due to osteoporosis have been observed
in patients with type 1 GD. Infiltration of Gaucher cells in the lungs leads
to pulmonary fibrosis and pulmonary arterial hypertension [56-59].
Patients with type 2 Gaucher disease showed severe neurological
impairment at 2– 6 months old, hepatosplenomegaly, rigidity of the neck
and trunk, bulbar signs, oculomotor paralysis and hypertonia [41].
Adult patients with type 3 Gaucher disease showed cerebellar
syndrome, mild splenomegaly, frontal myoclonic jerks, loss of intellectual
abilities, slight ophthalmoplegia, mild hepatomegaly, mild thrombopenia
and mental retardation [60]. While the normal subjects’ hemoglobin levels
range from 11-17 g%, GD patients hemoglobin levels are found to be
reduced. Wintrobe tube method showed packed cell volume range in
normal subjects’ is between 35-52%, while GD patients packed cell
volume is found to be reduced (Table 2).
Table 2. Analysis of blood in Gaucher disease patients
Age
Sex
Hemoglobin (g%)
Packed cell volume (%)
73
F
9.6
26
65
M
32
ND
60
M
9.6
28
58
F
10
28
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Parkinson’s Disease Association with Gaucher Disease …
263
9. PARKINSON’S DISEASE ASSOCIATION WITH
GAUCHER DISEASE
The GCase 1 gene is located on the long arm of chromosome 1q21
with 11 exons [61]. The enzyme deficiency leads to Gaucher disease, a
lysosomal storage disorder. GTP-binding protein type A1 (GBA1) encodes
GCase 1. Mutations in the GBA1 gene may degrade the protein, disrupting
lysosomal targeting and decreased performance of the enzyme in the
lysosome [62]. More than five hundred mutations have been identified in
the GBA1 gene. The gene mutations N370S, L444P, IVS2 + 1G > A,
V394L, and R496H [63-66] resulting enzyme deficiency also involved in
the cause of pathophysiology seen in PD. The L444P and W378R
mutations have been related with the cause of severe form of PD
pathophysiology [67-69]. Both patients with Gaucher disease and
heterozygous carriers are at increased risk of developing Parkinson disease
and Dementia. Patients with sporadic Parkinson disease have decreased
glucocerebrosidase activity. Deficiency of glucocerebrosidase activity
resulting lysosomal dysfunction and mitochondrial disorder contributes to
PD pathophysiology [70-71]. Motor, cognitive, olfactory and psychiatric
symptoms [72] are more severe in glucocerebrosidase mutation resulting
severe enzyme deficiency and Gaucher Disease-PD compared to mild
glucocerebrosidase mutation resulting enzyme deficiency and idiopathic
PD.
10. EFFECTS AND SIDE EFFECTS OF
PARKINSON’S DISEASE THERAPY
Invasive treatments such as application of chronic subthalamic nucleus
stimulation in patients with PD improved musculoskeletal pain and
dystonic pain with long-term pain relief [73]. In contrast, in patients with
peripheral neuropathic pain they observed a worsening of the peripheral
neuropathic pain. Subthalamic nucleus stimulation was effective in patients
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S. Rajasankar, V. Venkateshgobi and S. Surendran
264
with dystonic pain [74]. Bilateral pallidotomy also improved pain [75-76].
To avoid invasive treatments in patients with PD, noninvasive drugs
effects have been studied.
Music therapy improved depression seen in patients with PD. Patients
with physical therapy showed decrease in Dynamic Gait Index percentage.
The evaluation of patients by Romberg's test showed the positive results
compared with patients above fifty percentage needed help to complete the
task. After physical therapy classes the percentage decreased. Patients
static balance improved significantly [77].
Botulinum neurotoxin blocks the release of acetylcholine at the
neuromuscular junction to reduce pain and therefore used as a safe and
effective treatment for spasticity in various diseases including stroke, and
spinal cord injury, tremor, multiple sclerosis and dystonia [78]. It was
prescribed in the treatment of both dystonic and central pain.
Dopamine replacement therapy (L-DOPA, dopamine agonists,
monoamine oxidase B inhibitors and catechol-O-methyltransferase
inhibitors) have been used to improve dyskinesias, motor and non-motor
symptoms. Treatment of non-motor symptoms in PD includes
antidepressants, hypnotics, analgesics, anxiolytics, antidementive agents
and drugs for autonomic dysfunction [79]. Pimavanserin, quetiapine and
clozapine were useful in treating PD psychosis [80]. Regulating autophagy
pathway is one of the therapeutic options to protect cells against toxicity of
aggregate-prone proteins in neurodegenerative diseases [81].
11. EFFECTS AND SIDE EFFECTS OF
GAUCHER DISEASE THERAPY
Several enzymes are available such as Imiglucerase, alglucerase,
Cerezyme (Genzyme), Vpriv (Shire) and Elelyso (Pfizer). Enzyme
replacement therapy was found to be effective in treating patients with GD
with a dose of 15–30 U/kg/month. Application of lower doses 2.3 U/Kg
three times weekly or 30 U/Kg/month did not give much difference
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Parkinson’s Disease Association with Gaucher Disease …
265
compared to higher doses 120 U/Kg/Month [82]. However, enzyme
replacement therapy shows less effect on neurological abnormalities seen
in GD [83].
To reduce the levels of glucocerebrosidase substrate, glucosyl-
ceramide, substrate reduction therapy was attempted. Oral administration
of Miglustat (Actelion) is effective in reversing clinical symptoms seen in
mild to moderate disease type I Gaucher patients [84]. However, Miglustat
causes diarrhea, flatulence and abdominal pain/discomfort [85]. Oral
administration of Eliglustat (Genzyme), the substrate inhibitor, showed
improvement on patients with type 1 Gaucher patients.
CONCLUSION
Parkinson’s disease is a neurodegenerative disorder. Several factors
have been reported in the cause of PD pathophysiology. N-acetyl-L-
aspartic acid is found to be slightly elevated in the brain of patients with
PD. Glucocerebrosidase gene mutations resulting enzyme deficiency seen
in Gaucher disease, a lysosomal storage disorder, also contributes to PD
pathophysiology. However, glucocerebrosidase enzyme deficiency may
not be a common factor in treating PD.
REFERENCES
[1] Tysnes, OB, Storstein, A. Epidemiology of Parkinson’s disease. J.
Neural. Transm. (Vienna) 2017, 124, 901–905.
[2] Grosset, D, Antonini, A, Canesi, M, Pezzoli, G, Lees, A, Shaw, K,
Cubo, E, Martinez- Martin, P, Rascol, O, Negre-Pages, L, Senard, A,
Schwarz, J, Strecker, K, Reichmann, H, Storch, A, Löhle, M,
Stocchi, F, Grosset, K. Adherence to antiparkinson medication in a
multicenter European study. Mov. Disord. 2009, 24, 826–832.
https://t.me/medicina_free
S. Rajasankar, V. Venkateshgobi and S. Surendran
266
[3] Skorvanek, M, Gdovinova, Z, Rosenberger, J, Saeedian, RG,
Nagyova, I, Groothoff JW, van Dijk, JP. The associations between
fatigue, apathy, and depression in Parkinson's disease. Acta Neurol.
Scand. 2015, 131, 80–87.
[4] Valldeoriola, F, Coronell, C, Pont, C, Buongiorno, MT,Cámara,
A,Gaig, C, Compta, Y, ADHESON Study Group. Socio-
demographic and clinical factors influencing the adherence to
treatment in Parkinson's disease: the ADHESON study: socio-
demographic and clinical factors in treatment of Parkinson's disease.
Eur. J. Neurol. 2011, 18, 980–987.
[5] Herlofson, K, Kluger, BM. Fatigue in Parkinson's disease. J. Neurol.
Sci. 2017, 374, 38–41.
[6] Nègre-Pagès, L, Regragui, W, Bouhassira, D, Grandjean, H, Rascol,
O, DoPaMiP Study Group. Chronic pain in Parkinson’s disease: the
cross-sectional French DoPaMiP survey. Mov. Disord. 2008, 23,
1361–1369.
[7] Singleton, AB, Farrer, MJ, Bonifati, V. The genetics of Parkinson's
disease: progress and therapeutic implications. Mov. Disord. 2013,
28: 14–23.
[8] Bras, J, Guerreiro, R, Hardy, J. SnapShot: genetics of Parkinson's
disease. Cell. 2015, 160, 570.e1.
[9] Verstraeten, A, Theuns, J, Van Broeckhoven, C. Progress in
unraveling the genetic etiology of Parkinson disease in a genomic
era. Trends Genet. 2015, 31: 140–149.
[10] Han, QW, Yuan, YH, Chen, NH. The therapeutic role of cannabinoid
receptors and its agonists or antagonists in Parkinson's disease. Prog.
Neuropsychopharmacol. Biol. Psychiatry. 2019, 20, 109745.
[11] Jacobson, HB. Studies on the role of N-acetylaspartic acid on
mammalian brain. J. Gen. Physiol. 1957, 43, 323-333.
[12] Birken, DL, Olendorf, WH. N-acetyl aspartic acid: a literature review
of a compound prominent in 1H-NMR spectroscopic studies of brain.
Neurosci. Biobehav. Rev. 1989, 13, 23-31.
[13] Surendran, S, Kumaresan, G. Neurochemical changes and therapeutic
approaches in Canavan disease. In: Surendran S, editor.
https://t.me/medicina_free
Parkinson’s Disease Association with Gaucher Disease …
267
Neurochemistry of metabolic diseases: lysosomal storage diseases,
phenylketonuria and canavan disease: Trivandrum, India:
Transworld research network, 2007, pp 119-132.
[14] Surendran, S, Kaya, N, Ozand, P. Canavan disease: molecular
pathology, phenotype and therapeutic approaches. In: Surendran S,
editor. Neurochemistry of metabolic diseases: lysosomal storage
diseases, phenylketonuria and canavan disease: New York, USA:
NOVA science publishers, 2012, pp 241-263.
[15] D’Adamo, AF, Jr, Yatsu, FM. Acetate metabolism in the nervous
system. N-acetyl-L- aspartic acid and the biosynthesis of brain lipids.
J. Neurochem. 1966, 13, 961–965.
[16] Surendran, S, Bhatnagar, M. Upregulation of N-acetylaspartic acid
induces oxidative stress to contribute in disease pathophysiology. Int.
J. Neurosci. 2011, 121, 305-309.
[17] Surendran S. Upregulation of N-acetylaspartic acid resulting nitric
oxide toxicity induces aspartoacylase mutations and protein
interaction to cause pathophysiology seen in Canavan disease. Med.
Hypotheses. 2010, 75, 533-534.
[18] Surendran, S. Upregulation of N-acetylaspartic acid alters
inflammation, transcription and contractile associated protein levels
in the stomach and smooth muscle contractility. Mol. Biol. Rep.
2009, 36, 201-206.
[19] Surendran, S, Kondapaka, SB. Altered expression of neuronal nitric
oxide synthase in the duodenum longitudinal muscle-myenteric
plexus of obesity induced diabetes mouse: implications on enteric
neurodegeneration. Biochem. Biophys. Res. Commun. 2005, 338,
919-922.
[20] Robak, LA, Jansen, IE, van Rooij, J, Uitterlinden, AG, Kraaij, R,
Jankovic, J, International Parkinson’s Disease Genomics Consortium
(IPDGC), Heutink P, Shulman JM. Excessive burden of lysosomal
storage disorder gene variants in Parkinson's disease. Brain. 2017,
140, 3191-3203.
[21] Santiago, JA, Littlefield, AM, Potashkin, JA. Integrative
transcriptomic meta-analysis of Parkinson’s disease and depression
https://t.me/medicina_free
S. Rajasankar, V. Venkateshgobi and S. Surendran
268
identifies NAMPT as a potential blood biomarker for de novo
Parkinson’s disease. Sci. Rep. 2016, 6, 34579.
[22] Noyce, AJ, Bestwick, JP, Silveira-Moriyama, L, Hawkes, CH,
Giovannoni, G, Lees, AJ, Schrag, A. Meta-analysis of early
nonmotor features and risk factors for Parkinson disease. Ann.
Neurol. 2012, 72, 893–901.
[23] De Lau, LML, Koudstaal, PJ, Hofman, A, Breteler, MMB. Serum
uric acid levels and the risk of Parkinson disease. Ann. Neurol. 2005,
58, 797–800.
[24] Fernández-Santiago, R, Iranzo, A, Gaig, C, Serradell, M, Fernández,
M, Tolosa, E, Santamaría, J, Ezquerra, M. MicroRNA association
with synucleinopathy conversion in rapid eye movement behavior
disorder. Ann. Neurol. 2015, 77, 895–901.
[25] Suwijn, SR, van Boheemen, CJ, de Haan, RJ, Tissingh, G, Booij, J,
de Bie, RM. The diagnostic accuracy of dopamine transporter
SPECT imaging to detect nigrostriatal cell loss in patients with
Parkinson’s disease or clinically uncertain parkinsonism: a
systematic review. EJNMMI. Res. 2015, 5, 12.
[26] LeWitt, P. Recent advances in CSF biomarkers for Parkinson's
disease. Parkinsonism Relat. Disord. 2012, 18 Suppl 1, S49-51.
[27] Qiang, JK, Wong, YC, Siderowf, A, Hurtig, HI, Xie, SX, Lee, VM,
Trojanowski, JQ, Yearout, D, Leverenz, J, Montine, TJ, Stern, M,
Mendick, S, Jennings, D, Zabetian, C, Marek, K, Chen-Plotkin, AS.
Plasma apolipoprotein A1 as a biomarker for Parkinson disease. Ann.
Neurol. 2013, 74, 119–127.
[28] Shahnawaz, M, Tokuda, T, Waragai, M, Mendez, N, Ishii, R,
Trenkwalder, C, Mollenhauer, B, Soto, C. Development of a
Biochemical Diagnosis of Parkinson Disease by Detection of α-
Synuclein Misfolded Aggregates in Cerebrospinal Fluid. JAMA.
Neurol. 2017, 74, 163-172.
[29] Raccagni, C, Nonnekes, J, Bloem, BR, Peball, M, Boehme, C, Seppi,
K, Wenning, GK. Gait and postural disorders in parkinsonism: a
clinical approach. J. Neurol. 2019, doi: 10.1007/s00415-019-09382-
1.
https://t.me/medicina_free
Parkinson’s Disease Association with Gaucher Disease …
269
[30] Byun, JH, Cho, H, Kim, YJ, Kim, JS, Baik, JS, Jang, S, Ma, HI.
Trends in the Prevalence of Drug-Induced Parkinsonism in Korea.
Yonsei. Med. J. 2019, 60, 760-767.
[31] Waldthaler, J, Timmermann, L. Update on diagnostics and therapy of
idiopathic Parkinson's disease. Fortschr. Neurol. Psychiatr. 2019, 87,
445-461.
[32] Niemann, N, Jankovic, J. Juvenile parkinsonism: Differential
diagnosis, genetics, and treatment. Parkinsonism Relat. Disord. 2019,
67,74-89.
[33] Marsili, L, Bologna, M, Kojovic, M, Berardelli, A, Espay, AJ,
Colosimo, C. Dystonia in atypical parkinsonian disorders.
Parkinsonism Relat. Disord. 2019, 66, 25-33.
[34] Hruska, KS, LaMarca, ME, Scott, CR, Sidransky, E. Gaucher
disease: Mutation and polymorphism spectrum in the
glucocerebrosidase gene (GBA). Hum. Mutat. 2008, 29, 567–583.
[35] Hill, SC, Reinig, JW, Barranger, JA, Fink, J, Shawker, TH. Gaucher
disease: sonographic appearance of the spleen. Radiology. 1986, 160,
631-634.
[36] Neudorfer, O, Hadas-Halpern, I, Elstein, D, Abrahamov, A, Zimran,
A. Abdominal ultrasound findings mimicking hematological
malignancies in a study of 218 Gaucher patients. Am. J. Hematol.
1997, 55, 28-34.
[37] Stirnemann, J, Vigan, M, Hamroun, D, Heraoui, D, Rossi-Semerano,
L, Berger, MG, Rose, C, Camou, F, de Roux-Serratrice, C, Grosbois,
B, Kaminsky, P, Robert, A, Caillaud, C, Froissart, R, Levade, T,
Masseau, A, Mignot, C, Sedel, F, Dobbelaere, D, Vanier, MT,
Valayanopoulos, V, Fain, O, Fantin, B, de Villemeur, TB, Mentré, F,
Belmatoug, N. The French Gaucher's disease registry: clinical
characteristics, complications and treatment of 562 patients.
Orphanet. J. Rare Dis. 2012, 7, 77.
[38] Kaplan, P, Andersson, HC, Kacena, KA, Yee, JD. The clinical and
demographic characteristics of nonneuronopathic Gaucher disease in
887 children at diagnosis. Arch. Pediatr. Adolesc. Med. 2006, 160,
603-608.
https://t.me/medicina_free
S. Rajasankar, V. Venkateshgobi and S. Surendran
270
[39] Wenstrup, RJ, Roca-Espiau, M, Weinreb, NJ, Bembi, B. Skeletal
aspects of Gaucher disease: a review. Br. J. Radiol. 2002, 75 Suppl 1,
A2-12.
[40] Sidransky, E. Gaucher disease: Insights from a rare Mendelian
disorder. Discov. Med. 2012, 14, 273–281.
[41] Mignot, C, Doummar, D, Maire, I, De Villemeur, TB. French Type 2
Gaucher Disease Study Group Type 2 Gaucher disease: 15 new cases
and review of the literature. Brain Dev. 2006, 28, 39–48.
[42] Tylki-Szymańska, A, Vellodi, A, El-Beshlawy, A, Cole, JA,
Kolodny, E. Neuronopathic Gaucher disease: demographic and
clinical features of 131 patients enrolled in the International
Collaborative Gaucher Group Neurological Outcomes Subregistry. J.
Inherit. Metab. Dis. 2010, 33, 339-346.
[43] Kraoua, I, Sedel, F, Caillaud, C, Froissart, R, Stirnemann, J,
Chaurand, G, Flodrops, H, Tari, S, Gourfinkel-An, I, Mathieu, S,
Belmatoug, N, Billette de Villemeur, T, Mignot, C. A French
experience of type 3 Gaucher disease: Phenotypic diversity and
neurological outcome of 10 patients. Brain Dev. 2011, 33, 131-139.
[44] Mullin, S, Beavan, M, Bestwick, J, McNeill, A, Proukakis, C, Cox,
T, Hughes, D, Mehta, A, Zetterberg, H, Schapira, AHV. Evolution
and clustering of prodromal parkinsonian features in GBA1 carriers.
Mov. Disord. 2019, 34, 1365-1373.
[45] Yoshida, S, Kido, J, Matsumoto, S, Momosaki, K, Mitsubuchi, H,
Shimazu, T, Sugawara, K, Endo, F, Nakamura, K. Prenatal diagnosis
of Gaucher disease using next-generation sequencing. Pediatr. Int.
2016, 58, 946-949.
[46] Hollak, CE, van Weely, S, van Oers, MH, Aerts, JM. Marked
elevation of plasma chitotriosidase activity. A novel hallmark of
Gaucher disease. J. Clin. Invest. 1994, 93, 1288-1292.
[47] Bargagli. E, Bennett, D, Maggiorelli, C, Di Sipiom P, Margolliccim
M, Bianchim N, Rottolim P. Human chitotriosidase: a sensitive
biomarker of sarcoidosis. J. Clin. Immunol. 2013, 33, 264-270
[48] Boot, RG, Verhoek, M, de Fost, M, Hollak, CE, Maas, M,
Bleijlevens, B, van Breemen, MJ, van Meurs, M, Boven, LA, Laman,
https://t.me/medicina_free
Parkinson’s Disease Association with Gaucher Disease …
271
JD, Moran, MT, Cox, TM, Aerts, JM. Marked elevation of the
chemokine CCL18/PARC in Gaucher disease: a novel surrogate
marker for assessing therapeutic intervention. Blood. 2004, 103, 33-
39.
[49] Deegan, PB, Moran, MT, McFarlane, I, Schofield, JP, Boot, RG,
Aerts, JM, Cox, TM. Clinical evaluation of chemokine and
enzymatic biomarkers of Gaucher disease. Blood Cells Mol. Dis.
2005, 35, 259-267.
[50] Dekker, N, van Dussen, L, Hollak, CE, Overkleeft, H, Scheij, S,
Ghauharali, K, van Breemen, MJ, Ferraz, MJ, Groener, JE, Maas, M,
Wijburg, FA, Speijer, D, Tylki- Szymanska, A, Mistry, PK, Boot,
RG, Aerts, JM. Elevated plasma glucosylsphingosine in Gaucher
disease: relation to phenotype, storage cell markers, and therapeutic
response. Blood. 2011, 118, e118-127.
[51] Terroba-Chambi, C, Bruno, V, Millar-Vernetti, P, Bruce, D,
Brockman, S, Merello, M, Starkstein, S. Design and validation of a
new instrument to assess fear of falling in Parkinson's disease. Mov.
Disord. 2019, doi: 10.1002/mds.27820.
[52] Gál, O, Poláková, K, Hoskovcová, M, Tomandl, J, Čapek, V, Berka,
R, Brožová, H, Šestáková, I, Růžička, E. Pavement patterns can be
designed to improve gait in Parkinson's disease patients. Mov.
Disord. 2019, 34, 1831-1838.
[53] Suzuki, K, Fujita, H, Watanabe, Y, Matsubara, T, Kadowaki, T,
Sakuramoto, H, Hamaguchi, M, Nozawa, N, Hirata, K. Leg
restlessness preceding the onset of motor symptoms of Parkinson
disease: A case series of 5 patients. Medicine (Baltimore). 2019, 98,
e16892.
[54] Barone, P, Antonini, A, Colosimo, C, Marconi, R, Morgante, L,
Avarello, TP, Bottacchi, E, Cannas, A, Ceravolo, G, Ceravolo, R,
Cicarelli, G, Gaglio, RM, Giglia, RM, Iemolo, F, Manfredi, M,
Meco, G, Nicoletti, A, Pederzoli, M, Petrone, A, Pisani, A, Pontieri,
FE, Quatrale, R, Ramat, S, Scala, R, Volpe, G, Zappulla, S,
Bentivoglio, AR, Stocchi, F, Trianni, G, Dotto, PD, PRIAMO study
group. The PRIAMO study: a multicenter assessment of nonmotor
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