The Study Of Clinical Characteristics And Glycyl-tRNA Synthetase Gene Mutations In Adolescent-onset Myoatrophy Of Bilateral Distal Upper Extremities With Knee-jerk Hyperreflexia

Background:Adolescent—onset bilateral distal upper extremities muscular atrophy is an uncommon clinical entity,which includes Juvenile muscular atrophy of the distal upper extremity(JMADUE,also named Hirayama disease),Charcot-Marie-Tooth disease type 2D(CMT2D),and motor neuron disease(such as distal spinal muscular atrophy typeⅤ(dSMAV) and amyotrophic lateral sclerosis(ALS)).We have encountered five cases of young bilateral distal upper extremities muscular atrophy with Knee-jerk hyperreflexia.These patients are characterized by adolescent-onset bilateral weakness and myoatrophy in hand with Knee-jerk hyperreflexia, as well as slowly progressive aggravation.The clinical manifestations exhibited by these patients are different from Hirayama disease,CMT2D, and dSMAV.To make a definitely diagnosis,we carefully analyzed their clinical data and sequenced the fragment containing 10 mutations reported of the gene for glycyl-tRNA synthetase(GARS gene).Objective:To explore the association of adolescent—onset bilateral distal upper extremities muscular atrophy with GARS gene mutation and to help make a definitely diagnosis. Materials and Methods:1.A retrospective review and analysis was performed to the five patients with adolescent—onset bilateral distal upper extremities muscular atrophy,consisting of clinical characteristics,the determination of thyroid function,chest X-ray,electroneuromyography, head and cervical MRI.2.RNA was extracted by standard methods from fresh blood samples of the five patients and 15 healthy controls.RT-PCR and sequencing were performed to detect the 10 known mutations of GARS gene.Results:1.All five patients were characterized by adolescent-onset slowly progressive muscle weakness and atrophy,preferentially involving the muscles of bilateral distal upper extrimities,particularly the thenar eminence and first dorsal interossei muscles.Bilateral knee-jerks of five patients were increased.Electroneuromyography examination showed a neurogenic damage in all patients,involving the anterior horn cells of spinal cord.Conventional cervical MRI and flexed cervical MRI did not find abnormal lesions.2.GARS gene detection did not find abnormal mutations in the 10 known mutations sites.Conclusion:1.Adolescent-onset bilateral distal upper extremilties muscular atrophy with knee-jerk hyperreflexia is a rare disease of the nervous system.The clinical manifestations exhibited by these patients are different from Hirayama disease,CMT2D,and dSMAV.2.GARS gene sequencing did not find abnormal mutations in 10 known gene mutation sites.It indicates that these patients suffer from CMT2D/dSMAV with few possible.It needs DNA microarray detection to find the Candidate mutation gene furtherly.