Department of Neurology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
BMC Neurol. 2023 Jun 10;23(1):226. doi: 10.1186/s12883-023-03269-5.
The glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) genes are associated with the risk of sporadic Parkinson's disease (PD). As an environmental factor, hypoxic insults may impair dopamine neurons in the substantia nigra and exacerbate PD symptoms. However, covariants of GBA and LRRK2 combined with hypoxic insults in clinical cases of Parkinsonism have not yet been reported.
A 69-year-old male patient with PD and his relatives were clinically characterized and sequenced using the whole-exome technique. A novel covariant, c.1448 T > C (p. L483P, rs421016) on GBA and c.691 T > C (p. S231P, rs201332859) on LRRK2 were identified in this patient who first developed bradykinesia and rigidity in the neck at one month after an acute hypoxic insult during mountaineering. The patient presented with a mask-like face, festinating gait, asymmetric bradykinesia, and moderate rigidity. These symptoms were treated with levodopa and pramipexole, resulting in a 65% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. These parkinsonian symptoms persisted and developed with hallucinations, constipation, and rapid eye movement sleep behavior disorder. After 4 years, the patient exhibited a wearing-off phenomenon and died from pulmonary infection 8 years after disease onset. His parents, wife, and siblings were not diagnosed with PD, and his son carried p. L483P without Parkinsonism-like symptoms.
This is a case report of PD after hypoxic insult in a patient carrying a covariant of GBA and LRRK2. This study may help us understand the interaction between genetic and environmental factors in clinical PD.
葡萄糖脑苷脂酶（GBA）和富含亮氨酸重复激酶 2（LRRK2）基因与散发性帕金森病（PD）的风险相关。作为环境因素，缺氧损伤可能会损害黑质中的多巴胺神经元并加重 PD 症状。然而，尚未有报道在帕金森病病例中，GBA 和 LRRK2 的变异与缺氧损伤相关。
一名 69 岁男性 PD 患者及其亲属进行了临床特征分析和外显子组测序。该患者在登山时发生急性缺氧损伤一个月后首次出现颈部运动迟缓伴僵硬，随后出现了新的变异，GBA 上的 c.1448T > C（p. L483P，rs421016）和 LRRK2 上的 c.691T > C（p. S231P，rs201332859）。患者表现为面具脸、拖曳步态、不对称性运动迟缓伴中度僵硬。这些症状通过左旋多巴和普拉克索治疗，使统一帕金森病评定量表（UPDRS）运动评分改善了 65%。这些帕金森病症状持续存在并发展为幻觉、便秘和快速眼动睡眠行为障碍。4 年后，患者出现剂末现象，在发病 8 年后死于肺部感染。他的父母、妻子和兄弟姐妹均未被诊断为 PD，他的儿子携带 p. L483P，但没有出现类似帕金森病的症状。
这是一例 GBA 和 LRRK2 变异携带者在缺氧损伤后发生 PD 的病例报告。本研究可能有助于我们理解遗传和环境因素在临床 PD 中的相互作用。
