The close relationship between a rare disease and a common disease: Case report of a patient with gaucher disease and parkinsonism.
The close relationship between a rare disease and a common disease: Case report of a patient with gaucher disease and parkinsonism.
Where did the research take place?
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Augusto Corrêa, BR · Author affiliation
Inborn Errors of Metabolism Laboratory (LEIM) , Institute of Biological Sciences (ICB) / Federal University of Pará (UFPA), Rua Augusto Correa 1 - Guamá University Campus, Belém, PA, 66075-110, Brazil.Location evidence
BR · Author affiliation · country only
Experimental Neuropathology Laboratory (LANEX), Federal University of Pará, Belém, Brazil.Location evidence
Porto Alegre, BR · Author affiliation
Brazilian Rare Disease Network, Porto Alegre, Brazil. lcss@ufpa.br.Location evidence
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Original abstract
Gaucher disease (GD) is a lysosomal storage disorder caused by pathogenic variants in the GBA1 gene, which encodes glucocerebrosidase. GBA1 variants are also the most common genetic risk factor for Parkinson's disease (PD), although the penetrance of parkinsonism among carriers is incomplete. Patients with GD who develop parkinsonism may present an earlier onset and a more severe clinical course than individuals with sporadic PD. However, clinical data from underrepresented populations, including the Brazilian Amazon, remain scarce. We report the case of a 51-year-old woman from Belém, Pará, Brazil, diagnosed with GD type 1 and carrying the compound heterozygous GBA1 genotype p.N409S/p.L483P. The patient had been receiving substrate reduction therapy with miglustat when early parkinsonian manifestations were identified. Neurological examination revealed bradykinesia, rigidity of the left lower limb, and prominent postural and balance impairment, with an unstable gait and dysdiadochokinesia, in the absence of resting, kinetic, postural, or jaw tremor. Non-motor symptoms included sleep disturbances, paresthesia, and constipation. The clinical presentation was considered suggestive of an atypical parkinsonian phenotype, however, a definitive diagnosis of PD could not yet be established, and a levodopa trial is planned to evaluate treatment responsiveness and support diagnostic clarification. This case contributes clinical and molecular data on GBA1-associated parkinsonian manifestations from the Brazilian Amazon, an underrepresented population in genetic and clinical studies. The early and atypical motor phenotype, characterized by prominent postural and balance impairment without tremor, highlights the clinical heterogeneity of parkinsonism in the context of GD and GBA1 variants. The emergence of parkinsonian signs after prolonged substrate reduction therapy with miglustat also raises questions regarding the relationship between GD treatment and neurological outcomes, although no causal inference can be drawn from a single case. This case underscores the importance of longitudinal neurological surveillance and multidisciplinary follow-up of individuals with GD, while highlighting the need for further studies integrating genetic background, clinical phenotype, treatment exposure, and neurological progression.