Introduction to early onset Parkinson's disease

Introduction

Early onset Parkinson's disease

Clinical significance:

Genetic testing is helpful for the diagnosis of diseases, and has important reference value for studying the relationship between different gene mutation sites and clinical features, as well as clinical intervention and genetic guidance.

Etiology and clinical manifestations:

Parkinson's Disease(Parkinson's disease, PD) is a common neurodegenerative disease in the elderly. Generally, PD with an onset age of 50 or less is called early-onset Parkinsonism (EOP). In addition to the general clinical features of Parkinson's disease, the disease also has its own characteristics, such as symptoms of morning lightness and weight loss after sleep, dystonia, early prone to severe dopa-induced dyskinesia. EOP often has a tendency to familial aggregation and is closely related to mutations in the parkin gene (also known as the PARK2 gene). The Parkin gene encodes an E3 ubiquitin ligase that participates in the ubiquitin proteasome pathway, catalyzes the ubiquitination of abnormal proteins and promotes the degradation of abnormal proteins by the proteasome. Mutation of the parkin gene can attenuate the activity of the ligase, resulting in the accumulation of the substrate protein of parkin in the cell. The accumulation of these abnormal proteins has obvious toxic effects on neuronal cells, especially dopaminergic cells.

Genetic characteristics and incidence:

EOP is an autosomal recessive disorder in which the frequency of parkin gene mutations is 1.33-66% in EOP patients, while the frequency of parkin gene mutations in sporadic EOP patients is 1.75-21%. The parkin gene is one of the longest known genes (1.38 Mb), has abundant intron sequences, and is located in the most active fragile site (FRA6E) in the human genome, with high genomic instability. Therefore, the recombination rate of the parkin gene is high, accounting for about 50% of the parkin gene mutation.

Diagnosis and treatment:

The clinical symptoms of the disease are easily confused with many other syndromes. Therefore, according to the clinical symptoms, it is necessary to combine the genetic test for diagnosis, which is helpful for early intervention of patients. At present, the treatment of Parkinson's disease is based on drugs, and the compoundLevodopaThe preparation is one of the commonly used drugs, and the early clinical effect is better.