PDF(Pubmed)
Abstract：
Amongst a cohort of 88 alkaptonuria (AKU) patients attending the United Kingdom National Alkaptonuria Centre (NAC), four unrelated patients had co-existing Parkinson\'s disease (PD). Two of the NAC patients developed PD before receiving nitisinone (NIT) while the other two developed overt PD during NIT therapy. NIT lowers redox-active homogentisic acid (HGA) and profoundly increases tyrosine (TYR). A further unpublished case of a Dutch patient with AKU and PD on deep brain stimulation is included in this report. A Pubmed search revealed a further five AKU patients with PD, all without NIT usage. The prevalence of PD in AKU in the NAC appears to be nearly 20-times higher than in the non-AKU population (p < 0.001) even when adjusted for age. We propose that life-long exposure to redox-active HGA may account for the higher prevalence of PD in AKU. Furthermore, the appearance of PD in AKU patients during NIT therapy may be due to unmasking dopamine deficiency in susceptible individuals, as a result of the tyrosinaemia during NIT therapy inhibiting the rate-limiting brain tyrosine hydroxylase.
摘要：
在英国国家碱性尿症中心（NAC）的88名碱性尿症（AKU）患者队列中，4例无关患者同时存在帕金森病（PD）。两名NAC患者在接受Nitisinone（NIT）之前发生了PD，而另外两名患者在NIT治疗期间发生了明显的PD。NIT降低了氧化还原活性的均质酸（HGA），并极大地增加了酪氨酸（TYR）。本报告还包括另一例未发表的荷兰患者在深部脑刺激下患有AKU和PD。Pubmed搜索显示另外五名患有PD的AKU患者，都没有使用NIT。NAC中AKU中PD的患病率似乎比非AKU人群高近20倍（p<0.001），即使根据年龄进行了调整。我们建议终身暴露于氧化还原活性HGA可能是AKU中PD患病率较高的原因。此外，在NIT治疗过程中，AKU患者出现PD可能是由于暴露易感个体的多巴胺缺乏，由于NIT治疗期间酪氨酸血症抑制了限速脑酪氨酸羟化酶。
