Lopez Grisel J, Lichtenberg Jens, Tayebi Nahid, Ryan Emory, Lecker Abigail L, Sidransky Ellen
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States.
Front Neurol. 2022 Oct 18;13:1039214. doi: 10.3389/fneur.2022.1039214. eCollection 2022.
Biallelic mutations in , which encodes the lysosomal enzyme glucocerebrosidase, cause the lysosomal storage disorder Gaucher disease (GD). In addition, mutations in are the most common genetic risk factor for future development of Parkinson's disease (PD). However, most mutation carriers will never develop parkinsonism. Olfactory dysfunction is often a prodromal symptom in patients with PD, appearing many years prior to motor dysfunction. The purpose of this study was to assess olfactory function longitudinally in individuals with and without parkinsonism who carry at least one mutation.
One hundred seventeen individuals who participated in a natural history study of GD at the National Institutes of Health were evaluated using the University of Pennsylvania Smell Identification Test (UPSIT) during a 16-year period. Seventy patients with GD (13 with PD) and 47 carriers (9 with PD) were included. Fifty-six of the total (47.9%) were seen over multiple visits, and had UPSIT screening performed two to six times, with time intervals between testing ranging from 2 to 6 years. Comparative and control data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database (519 individuals, including 340 with idiopathic PD and 179 healthy controls). Statistical analysis was performed using R.
Severe hyposmia and anosmia was evident in both heterozygotes and homozygotes with PD. 84% without parkinsonism had UPSIT scores >30, and those who underwent repeated testing maintained olfactory function over time. No statistically significant difference in UPSIT scores was found between mutation carriers with and without a family history of parkinsonism. A small group of individuals without PD scored in the moderate-severe microsmia range. No significant differences in olfaction were found among our -PD cohort and idiopathic PD cohort obtained from PPMI.
编码溶酶体酶葡萄糖脑苷脂酶的基因发生双等位基因突变会导致溶酶体贮积病戈谢病（GD）。此外，该基因突变是帕金森病（PD）未来发病最常见的遗传风险因素。然而，大多数突变携带者永远不会出现帕金森综合征。嗅觉功能障碍通常是PD患者的前驱症状，在运动功能障碍出现前数年就会出现。本研究的目的是纵向评估携带至少一个该基因突变且有或无帕金森综合征个体的嗅觉功能。
117名参与美国国立卫生研究院戈谢病自然史研究的个体在16年期间使用宾夕法尼亚大学嗅觉识别测试（UPSIT）进行评估。其中包括70例GD患者（13例患有PD）和47名该基因携带者（9例患有PD）。总共有56人（47.9%）接受了多次随访，进行了2至6次UPSIT筛查，测试时间间隔为2至6年。比较和对照数据来自帕金森病进展标志物倡议（PPMI）数据库（519人，包括340例特发性PD患者和179名健康对照）。使用R进行统计分析。
患有PD的该基因杂合子和纯合子均明显存在严重嗅觉减退和嗅觉丧失。84%无帕金森综合征的个体UPSIT评分>30，且接受重复测试的个体随时间保持嗅觉功能。有和无帕金森病家族史的突变携带者之间UPSIT评分无统计学显著差异。一小部分无PD的个体评分处于中度至重度嗅觉减退范围。在我们的非PD队列和从PPMI获得的特发性PD队列之间，嗅觉方面未发现显著差异。
