Study On Non-nervous System Clinical Phenotype And Biomarkers Of Spinal And Bulbar Muscular Atrophy

Objective:The purpose of this study is to research the non-nervous system clinical phenotype of spinal and bulbar muscular atrophy(SBMA)and analyze the laboratory parameters of neuromuscle,metabolism and endocrine,and to explore their correlation with the disease duration and the severity of the disease,so as to provide a basis for the selection of biomarkers in clinical treatment trials.Methods:(1)After the informed consent of the patients,the medical history and complications of 16 genetically diagnosed SBMA patients were obtained through structured interview.Multi-system clinical evaluation and examination were performed on all SBMA subjects.Patients are required to complete modified 12-lead electrocardiogram,standard two-dimensional doppler echocardiography,liver ultrasound,prostate ultrasound and muscle pathological examination.We need to study the incidence of brugada syndrome,nonalcoholic fatty liver disease(NAFLD)and lower urinary tract symptoms.(2)The prevalence of NAFLD was compared between the SBMA group and the healthy control group.(3)After informed consent of the subjects,fasting venous blood was collected to compare the differences of serum creatinine level between SBMA group and ALS group,and the difference of dehydroepiandrosterone sulfate(DHEAS)between SBMA group and healthy control group.(4)To study the correlation between laboratory parameters and the age of onset,the course of disease and the score of SBMA functional rating scale(SBMAFRS).Results:(1)Non-nervous system clinical phenotype1)Cardiac assessment and examination did not find brugada syndrome and brugada-like electrocardiogram(ECG)manifestations in 16 patients.13 patients(81.25%)did not have any clinical symptoms related to the heart,and 3 patients(18.75%)suffered from palpitation and chest tightness.The echocardiographic examinations of 16 patients were almost normal.The ECG examination of 12 patients(75%)showed no abnormality,2 patients(12.5%)showed incomplete right bundle branch block,and 1 patient(6.25%)showed sinus tachycardia.1 patient had severe symptoms of palpitation and chest tightness,and his ECG showed t-wave inversion in chest lead V2-V6 and limb leads ?,?,aVF,and no abnormality was found in cardiac coronary angiography.2)In the SBMA group,15 patients were included in the NAFLD study,and fatty liver was found in 11 patients(73.3%).Liver ultrasound revealed fatty liver in 4 of 15 healthy controls(26.67%).The prevalence rate of NAFLD in SBMA group was significantly higher than that in healthy control group,(P=0.01),the difference was statistically significant.3)Sixteen SBMA patients completed the international prostate symptom score questionnaire and prostate ultrasound examination,of which 9(56.25%)had no or mild symptoms of lower urinary tract symptoms and 7(43.75%)had moderate lower urinary tract symptoms.It was found that 13 patients(81.25%)had normal prostate volume and 3 patients(18.75%)had prostatic hypertrophy.Among them,5 patients(18.75%)had moderate lower urinary tract symptoms,but their prostate volume was normal.4)Skeletal muscle biopsy was carried out in 7 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed.(2)Laboratory parameters.1)Serum creatine kinase increased in 16 patients with SBMA.The levels of triglyceride in 10 patients(62.5%),low density lipoprotein cholesterol in 7 patients(43.75%)and serum total cholesterol in 5 patients(32.5%)were higher than normal.The serum creatinine level was decreased in 14 of 16 SBMA patients(87.5%).The average serum creatinine value in SBMA group was 43.54 ±9.56 umol / L.Serum creatinine level decreased in 1 of 16 ALS patients(6.25%).The average serum creatinine level in ALS group was 66.04 ±13.69 umol / L.The abnormal rate of serum creatinine in SBMA group was significantly higher than that in ALS group,and the average serum creatinine level in SBMA group was significantly lower than that in ALS group(P<0.001),The difference was statistically significant.2)Of the 10 patients who completed the sex hormone test,luteinizing hormone levels in 6 patients(60%)and estradiol levels in 3 patients(30%)were higher than normal.The average level of DHEAS in SBMA patients(261.25 ±54.96 ? g / dl,)was significantly higher than that in healthy controls(195.13 ±73.21 ? g / dl)(P=0.035),the difference was statistically significant.(3)The relationship between experimental parameters and the course of disease and SBMAFRS score1)DHEAS was negatively correlated with the age of onset of the first symptoms.Serum creatinine was negatively correlated with the course of disease and positively correlated with the age of onset of the first symptom and SBMAFRS score.2)There was no correlation between laboratory parameters such as creatine kinase,testosterone,luteinizing hormone,and dehydroepiandrosterone and the age of onset of the first symptom,duration of disease and SBMAFRS score.Conclusions:(1)Patients with SBMA have relatively specific liver involvement,and NAFLD may be another clinical phenotype of SBMA.(2)Patients with SBMA have lower urinary tract symptoms unrelated to the prostate.(3)Patients with SBMA have endocrine and metabolic syndrome.(4)Serum creatinine can be used as an effective biomarker to reflect the severity of SBMA disease.(5)DHEAS may be a potential biomarker of SBMA.