Koros Christos, Simitsi Athina-Maria, Papagiannakis Nikolaos, Bougea Anastasia, Antonelou Roubina, Pachi Ioanna, Sfikas Evangelos, Stanitsa Evangelia, Angelopoulou Efthalia, Constantinides Vasilios C, Papageorgiou Sokratis G, Potagas Constantin, Stamelou Maria, Stefanis Leonidas
1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece.
Hygeia Hospital, 15123 Athens, Greece.
Neurol Int. 2024 Jul 30;16(4):833-844. doi: 10.3390/neurolint16040062.
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.
Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous carriers, four heterozygous carriers, and three biallelic carriers) were evaluated.
The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in carriers and 765 ± 96.6 (range 660-850) in 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 and 1/3 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.
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.
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，疾病发作早且症状相对较轻。关于常染色体隐性遗传性帕金森病个体化治疗的数据仍然匮乏。
对一组隐性基因帕金森病携带者（9名纯合子或复合杂合子携带者、4名单杂合子携带者和3名双等位基因携带者）的人口统计学和治疗数据进行了评估。
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），携带者为765±96.6（范围660 - 850）。大多数患者对低/中等剂量的左旋多巴有反应。多巴胺激动剂（DAs）作为初始治疗和长期治疗通常效果良好。总共，8/13的携带者和1/3的携带者成功接受了金刚烷胺治疗，这也适用于不能耐受左旋多巴或多巴胺激动剂的患者。
在个性化治疗时代，隐性遗传性帕金森病基因携带者的治疗方法可能与特发性帕金森病不同。即使是病程很长的患者，较低的LEDD剂量也有效，而少数患者在疾病发作数十年后未接受任何左旋多巴治疗也状况良好。如果耐受性良好，多巴胺激动剂或金刚烷胺可作为一线主要治疗方案。关于隐性遗传性帕金森病基因致病突变携带者治疗策略的文献数据，包括器械辅助治疗，将进一步讨论。
