Parkinsonism Associated with Glucocerebrosidase Mutation

Abstract

BackgroundGaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations.Case ReportA 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen.ConclusionsThis case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation.

The link between the GBA gene and parkinsonism

“…Two sisters with Parkinson’s disease from South Korea, one with Gaucher's disease and one a carrier, were assessed with 18 F-N-fluoropropyl–2β-carbomethoxy-3β-(4-iodophenyl)nortropane PET at ages 44 years and 55 years, respectively. 70 Both showed decreased reuptake of dopamine in the posterior putamen, in a pattern similar to that noted in sporadic Parkinson’s disease. Four additional patients assessed with 18 F-fluorodopa PET also showed decreased striatal uptake.…”

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

“…There are 2 reports of DAT-SPECT in Gaucher disease patients with PD or PD patients with heterozygous GBA mutations [16], [17]. Though not formally quantified, inspection of the published images reveals clear asymmetry of radioligand uptake affecting the striatum.…”

Pathological Mechanisms and Clinical Aspects of GBA1 Mutation-Associated Parkinson’s Disease

“…Dopamine transporter PET imaging (DaTSCAN) using the dopamine transporter ligands 18F-fluoropropylcarbomethoxyiodophenylnortropane (18F-FP-CIT) and 123-ioflupane (123I-FP-CIT) have shown a greater degree of dopaminergic neuronal loss in PD associated with GBA1 mutation than in patients with wild-type GBA1 (84,(92)(93)(94). Asymmetry of radio ligand uptake is more pronounced in PD associated with GBA1 mutations than in some of the genetic forms of PD associated with a Mendelian inheritance pattern (SNCA, PINK1, or Parkin mutations) (92).…”