Analysis Of The Clinical, Pathology, Electrophysiology, Muscle MRI And Genetic Features Of Lipid Storage Myopathy

Objective To study the clinical, pathology, electrophysiology, muscle MRI and genetic features of lipid storage myopathy in order to learn more about this disorder, improving our diagnosis and treatment.Methods The clinical data of 33 patients with lipid storage myopathy confirmed by muscle biopsy or molecular analysis were collected. The sequences of ETFDH in all cases were analyzed by TP-PCR. Those negative ones underwent next generation sequencing.Results 1. All patients were subacute or chronic onset proximal muscle weakness accompanied by intolerance to exercise, 11/33（33.33%） patients show chewing muscle weakness, 4 of which dysmasesia was the first symptom; 9 /33（27.27%） patients present with difficulty to lift their head, 4/33（12.12%） had difficulty of breathing, 6 /33（18.18%） patients have abnormal feeling in their extremities. 2. 31/33（93.94%） patients were found to have elevated levels of muscle enzyme at 295-21401IU/L（normal range 24-195IU/L）. 3. 27 patients have completely electrophysiology data. Among them 14 patients revealed myopathic, 5 were pure sensory neuropathic, 1 was myopathic mixed sensory neuropathic, while the others were relatively normal. 4. 8/20 patients were confirmed MADD by MS/MS for analysis of acylcarnitine. And 9/18 patients were confirmed by GC-MS for urine organic acidemias as GAⅡ. 5. The muscle MRI of bilateral thighs in 12 patients show abnormal signal selectively affected the posterior groups. The abnormal signals were edema in the early stage. With the progression of the disease, they were partly fatty infiltration. The muscle impairment of patients with a longer duration or peripheral neuropathy progress faster.6. Muscle biopsy revealed lipid drops prominently in type Ⅰ fibers in 32 patients. On SDH staining, 7/32（21.88%） patients showed a diffused decrease or disappear of enzyme activity. While the other patient showed mild necrosis and regeneration. 7. Molecular analysis revealed 28/33（84.85%） patients with ETFDH mutation, which included 5 homozygosises, 9 compound heterozygosises, of which c.617A>G 、c.1258G>C、c.1313C>G、c.1484G>T and c.1555₁556del were new virations. 14 single heterozygosises, and c.1009T>C、c.109G>A and c.1281 del AA were new virations. Additionally, 1 patient carried a single heterozygosises mutation of SLC22A5（c.635T>A）, and 1 patient with a homozygous mutation of ACADVL（c.1283G>A）. While we haven’t found any gene defect in the other 3 patients.Conclusions Exercise intolerance, weakness of the neck and chewing muscle were characteristics of LSM, some patients may accompanied by sensory nerve impairment; Creatase range from normal to obviously elevated, and some patients may be misdiagnosed as polymyositis; Electrophysiology examination can reveal subclinical sensory nerve impairment. Muscle MRI of LSM show edema in the posterior compartment of the thighs, with the progression of the disease, fatty infiltration emerged in the epimysium and muscle sleeve. Those accompanied by peripheral nerve impairment showed severer atrophy. The MS/MS and GC/MS analysis of acylcarnitine and urine organic acidemias can help to diagnosis MADD, but the negative results can’t rule out the disease. Molecular analysis revealed the majority of patients in our research are MADD caused by ETFDH mutation, additionally, we found a SLC22A5 and ACADVL mutation, and there exist some pathogenic gene we don’t know yet.