Parkinson’s disease in a patient with GBA and LRRK2 covariants after acute hypoxic insult: a case report

Abstract

Abstract Background 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. Case presentation 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. Conclusions 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.