Clinical Analysis Of Spinal Muscular Atrophy Types 1-2 In 56 Children

Objective: By retrospectively analyzing the clinical characteristics of children with SMA type 1 and type 2,further raise understanding of the multi-system involvement of the disease,relationship between the clinical characteristics and genotype,and provide reference for better multi-disciplinary management and gene therapy.Methods: Retrospectively analyzed the clinical data of 56 children with SMA type 1 and type 2 admitted to the Children’s Hospital of Chongqing Medical University from November 2011 to August 2020,and analyzed the risk factors of influencing survival.Results: There are 56 patients with SMA type 1 and type 2,SMA type1 35 children and SMA type 2 21 children,male: female = 1.5:1.The onset age of the two types was 2.1 ± 1.7 months and 8.6 ± 3.4 months.The majority of initial manifestations was amyosthenia(89.3%).Pneumonia(10.7%),as an onset clinical feature,occurred in SMA type 1.The leading characteristics of SMA were muscle weakness,and hypomyotonia.Heading control unsteadily and crying weakness more occurred in SMA type 1(P = 0.001,P = 0.000).The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in patients with SMA type 1 were significantly higher than SMA type 2(P<0.05).Infection was more obvious in SMA type 1(P=0.000).The main respiratory pathogen in SMA were Acinetobacter baumannii(11.4%),Streptococcus pneumoniae(8.6%),Escherichia coli(8.6%),Moraxella cataraxis(8.6%).The absence CMAP is more often in SMA type 1(P=0.001),and decrease amplitude of CMAP was more often in SMA type 2(P=0.009).No obvious abnormalities were found in head MRI.By cardiac ultrasonography,the dominant heart anomaly of SMA was patent foramen ovale(63.3%).All SMA patients had homozygous deletion of exon 7 of SMN1 gene(100.0%).The dominant mutation was homozygous deletion of exon 7(82.1%).There was no difference in the detection rate of two types(P<0.05).In this study,only 4patients of SMN2 copy number detection were perfected,one patient with SMA type 1 had two copies of SMN2 gene,and three patients with SMA type 2 had three copies.The survival rate of SMA type 1 was significantly lower than that of SMA type 2(P=0.000).The 2-year survival rate of SMA type 1 was only 19.0%.Kaplan-Meier univariate survival analysis showed that the age of onset less than 3 months,the onset of pneumonia,head control unsteadily,infection and absence of CMAP amplitude was an independent risk factor for SMA type 1.By combination Cox multivariate analysis,we found the age of onset of less than 3 months and the onset of pneumonia were independent risk factors for SMA type 1 survival(P<0.05).Conclusion: Main initial symptom of spinal muscular atrophy was muscle weakness,and some was pneumonia.The lower extremity muscle weakness was more severe than the upper.Clinical phenotype of SMA was diverse and systematic.Respiratory,Cardiac abnormalities and digestive symptoms were relatively common among multisystem involvement.Since liver in patients with SMA type 1 was more vulnerable,reduction of exposure to liver damage as far as possible was suggested.Patients with SMA type 1 should avoid infection,especially nosocomial infection and infection of fungus and drug-resistance bacteria.CMAP amplitude can be a biomarker of evaluating disease severity and prognosis.All SMA patients had homozygous deletion of exon 7 of SMN1 gene,can be used for diagnosis of SMA.The survival rate of SMA type 1 was very low,only19.0% at 2 years.The age of onset less than 3 months and onset of pneumonia were independent risk factors of SMA type 1.