背景:携带隐性基因变异的帕金森病(PD)患者表现出独特的临床表型,具有早期疾病发作和相对轻度的症状。有关常染色体隐性遗传PD形式的个体化治疗的数据仍然很少。
方法:一组隐性基因PD携带者(9个纯合或复合杂合PRKN携带者,四个杂合PRKN携带者,和三个双等位基因PINK1携带者)进行了评估。
结果:PRKN携带者的平均左旋多巴等效日剂量(LEDD)为806.8±453.5(范围152-1810),PINK1携带者为765±96.6(范围660-850)。大多数人对低/中等剂量的左旋多巴有反应。作为初始和纵向治疗,对多巴胺激动剂(DA)的反应通常都是有利的。总的来说,8/13PRKN和1/3PINK1携带者用金刚烷胺成功治疗,这也适用于不能耐受左旋多巴或DA的患者。
结论:在个性化治疗的时代,与特发性PD相比,隐性PD基因携带者的治疗方法可能有所不同。即使在疾病持续时间很长的患者中,较低的LEDD剂量也是有效的,而一些患者在疾病开始几十年后没有任何左旋多巴治疗就表现良好。如果耐受性良好,DA或金刚烷胺可用作一线和主线治疗方案。关于隐性PD基因致病突变携带者治疗策略的文献数据,包括设备辅助治疗,将进一步讨论。
BACKGROUND: Parkinson\'s disease (PD) patients harboring
recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal
recessive PD forms are still scarce.
METHODS: Demographic and treatment data of a cohort of PD carriers of
recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated.
RESULTS: The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in PRKN carriers and 765 ± 96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.
CONCLUSIONS: In the era of personalized treatment, the therapeutic approach in
recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in
recessive PD genes, including device-aided treatments, will be further discussed.