Clinical Analysis Of Hereditary Spastic Paraplegia

Objective:To discuss the hereditary spastic paraplegia(HSP) in patients with clinical manifestations, further improve the cognition and understanding of the disease.Methods:We retrospectively analysed the clinical data of patients who was diagnosed hereditary spastic paraplegia between January 2003 to January 2015 in the First Affiliated Hospital of Guangxi Medical University. Through investigating one case of HSP in the family,determining its clinical classification and inheritance from the family history, gene mutation are screened in the proband and his family members of which methods are as follows:1. Collecting the clinical data of proband and family history, drawing family and standard were taken.2. Genetic testing: ①DNA from peripheral blood of the proband and his family members were extracted. ②The Next Generation Sequencing(NGS) of HSP were detected in the proband to obtain the candidate disease causing gene mutations. ③Sanger sequencing was performed in the other family members and compared with the exome of the pathogenic mutation of the proband.Results:Result:The 10 cases patients were all compled with the diagnostic criteria of Harding which can be diagnosed hereditary spastic paraplegia (HSP).There are 8 cases of male and 2 cases of female (male:female=4:1).The onset age ranged from 2-33 years old which the median age was 18 years and the course of disease was 8months-15 years which the median duration of 7 years.It is classified as pure HSP (5 cases) and complicated HSP (5 cases). The initial symptoms are mostly weakness of lower limbs. Complex HSP was ofen associated with mental decline (4/10). It is common in 10 cases of HSP patients which were scissors gait, muscle weakness, lower limbs muscle tension, knee reflex and ankle reflex enhancement.Auxiliary examination:10 cases HSP patients with blood, urine and stool routine and biochemical blood (liver and kidney function, myocardial enzymes, levels of fasting blood glucose, serum ceruloplasmin, vitamin B12 etc.) were in the normal range. There were 3 cases of cerebrospinal fluid examination showed no abnormality. Most of the patients with pure HSP showed no abnormality in head, cervical vertebrae and thoracic vertebrae MRI scan.1 cases of cervical MRI were slightly thinner cervical spinal cord.4 complicated HSP cases with cervical and thoracic and lumbar segments of the spinal cord and brain MRI examination showed no obvious abnormalities andl cases with cranial MRI showed demyelination of white matter and brain atrophy, magnetic resonance spectroscopy(MRS) and diffusion tensor imaging(DTI) showed no abnormalities.1 patients with complicated HSP with cranial MRI showed lateral frontal lobe symmetry thinning.1 cases showed mild abnormal EEG (EEG).1 the sensory and motor nerve conduction velocity of routine electromyography showed bilateral posterior tibial.somatosensory evoked potentials:the right lower extremity prolongation of N9 wave latency, the rest of the potential abnormal brainstem auditory evoked potential and so the visual is no abnormal. In one example of a clinical classification as pure HSP family, the proband (Ⅲ1) performed the NGS were found compound heterozygous mutations in Spastin gene:c.1685G>A,P.(Arg562Gln). The results of Sanger sequencing which performed in the genetic of 19 family members (peers with siblings of III 1 including 13 people and their4 offsprings,2 people from close family members of Ⅲ1 from the mother’s side) showed that the 2 surviving patients also had c.1685G>A,P.(Arg562Gln) heterozygous mutations and 7 family members of 17 other family members as gene carriers who respectively were Ⅲ3, Ⅲ 14, Ⅲ8, Ⅲ11, Ⅲ16, Ⅲ20, IV6.The 7 patients with incomplete penetrance, of which 2 cases of male, female 5 cases.Conclusion:Firstly, the onset age of hereditary spastic paraplegia patients in this team was the majority of childrens or adolescent and the first symptom wasfrequency with lower extremity weakness. Secondly, pure HSP in this group of patients underwent spastin gene detection showed significant genetic and clinical heterogeneity, incomplete penetrance, gender differences, anticipation phenomenon and other phenomena.