The Clinical, Pathological And Genetic Analysis Of Lipid Storage Myopathy

Objective1. To investigate the clinical and pathological features of lipid storage myopathy (LSM) patients and provide aids for diagnosis and treatment.2. To analyze the characteristics of LSM patients with respiratory paralysis and reduce clinical misdiagnosis.3. To explore the relationship between gene mutation and disease by detecting genes related with lipid metabolism. Methods1. Collect the clinical and pathological materials of 53 LSM and analyze features of them.2. Summarize the clinical and pathological features of LSM patients with respiratory paralysis.3. Detect gene mutation related with lipid metabolism in 22 LSM patients by the Next Generation Sequencing Technology.Results1. Most of LSM patients were young or mid-aged, and the mean onset age was 31.20±11.68 years. The ratio of male to female was 2.3:1. The initial symptoms of LSM was myasthenia with proximal of extremities(52.83%), intolerance of exercises (22.64%) as well as myalgia(7.55%),64.15% patients with onset in winter or spring.2. The elevation of enzyme appeared in 90.75% patients. The value of CK and LDH had no correlation with age, duration and onset age (P>0.05). Myogenic damage appeared in 70.59% cases, mixed type of damage in 3.92% cases and normal in 25.49% cases.3. The muscle histochemical staining indicated that 12 cases belong to severe-grade,13 cases were moderate,28 cases were mild. Muscle specimens showed numerous vacuoles accumulated in both types, with greater involvement of type I fibers.4. The male patients with respiratory paralysis were more than female. The patients aged from 14 to 39 years. The courses of disease ranged from 3 month to 4 years, with proximal muscle strength 1-5 grade. CK value fluctuated in 88.0-4609.6U/L.2 patients were mild LSM, and marked variation size necrosis muscle fibers were observed in the moderate (4 cases) and severe patients (2 cases).5. We observed 20 patients have ETFDH mutation.11 patients are presented with compound heterozygous mutation,5 patients with homozygous mutation and 4 patients with single heterozygous mutation. The mutation c.629A>G was most common (9/36, 25.00%), with the amino acid changes p.Y210C.1 patient had HADHB mutation and 1 patient had not detected gene mutation.Conclusion1. The study with occurrence 2.73% of LSM reveals that the majority of patients are male and sporadic. Onset age and duration are highly variable. Above 50% patients are presented with neck and bulbar muscle weakness. The severe the lipid droplets accumulate, the higher levels of muscle enzymes.2. The pathology of LSM patients with respiratory paralysis is inconsistent with clinical symptoms.3. The majority of LSM patients are multiple acyl-CoA dehydrogenase deficiency (MADD) and c.629A>G mutation in ETFDH gene is the most common.4. We detect new ETFDH gene mutations of LSM patients in China, including c.382C>T(p.R128C), c.1086A>C (p.L362F), c.844T>C (p.Y282H), c.1300delG (p.E434fs) and c.1220dupT (p.I407fs).