| Background and Purpose:autophagic vacuolar myopathies(AVMs)are a group of diseases associated by common histopathological features on muscle biopsies,including abnormal accumulation of autophagic vacuoles,typically due to advanced autophagy pathways,especially autophagosome maturation.The result is cell vacuolation and muscle fiber injury and atrophy.autophagy is a physiological catabolic process,in which redundant and aging substances in the cytoplasm,such as damaged organelle and abnormally folded protein,are fused through lysosomes and eventually degraded together with lysosomes.It is an important means for cells to maintain the normal physiological function of material and energy balance.When the autophagy pathway is abnormal,it can cause a variety of diseases.Classic diseases that constitute autophagy vacuolar myopathy include Pompe disease,Danon disease and X-linked myopathy with excessive autophagy(XMEA).Other diseases,including acquired myopathy(e.g.,chloroquine,colchicine poisoning,etc.),also have pathological features of autophagy myopathy.Some of these diseases not only co-exist autophagic vacuoles,but these autophagic vacuoles also have sarcolemmal features morphologic properties,thus making them autophagic vacuoles with sarcolemmal features(AVSFs),This is almost typical of this group of diseases.However,the clinical and pathological manifestations of different types of AVMs are also different,and the above different pathological changes suggest that the pathogenesis of these diseases may be different.Since these myopathies are very rare in China,and many myopathies that may have the same pathological changes have not been included in the concept of autophagy vacuolar myopathy,systematic summary is lacking.Therefore,the clinical manifestations,influence characteristics and pathological manifestations of 6 patients with AVM in Jiangxi area are reported,and this kind of disease is discussed.Materials and Methods:Six patients admitted to the Department of Neurology,The First Affiliated Hospital of Nanchang University from 2011 to 2022 were selected and confirmed as autophagy vacuolar myopathy by muscle biopsy,freezing routine chemical staining,enzyme histochemical staining,immunohistochemical staining and genetic examination.The clinical,imaging and pathological data of 1 patient with Pompe disease,1 patient with Danon disease,1 patient with XMEA disease and 3 patients with other unexplained autophagy vacuolar myopathy were analyzed.Results:1.Most of the AVM patients were younger,more than half of them had the onset in childhood or adolescence,with a long course of disease and sporadic onset without a clear family history.Pompe disease and Danon disease patients had more obvious symptoms of muscle damage outside skeletal muscles,which were respiratory muscle dysfunction and myocardial dysfunction,respectively,and had a cold before the onset.However,the main symptoms of other AVM patients were lower limb muscle damage,and the proximal muscle strength was poor.Two patients had signs of muscular atrophy.In most patients,serum creatine kinase was elevated,muscle magnetic resonance imaging showed abnormal signals of steatosis,and electromyography showed neurogenic and myogenic damage.Pathogenic mutations were found in Pompe disease and XMEA patients.2.Muscle biopsy pathological results of AVM patients generally showed that some muscle fibers had atrophy,hypertrophy and other morphological changes,and there was no obvious proliferation of surrounding connective tissue,no obvious necrosis and inflammatory cell infiltration.In Pompe disease and Danon disease,there is glycogen deposition in the vacuoles,but there is no outer membrane coating in Pompe disease.Other AVM muscle pathology has the characteristic autophagic vacuoles with saromyosis characteristics,and obvious outer membrane protein expression.MHCI and C5b9 immune complexes were also deposited outside the vacuoles of some AVM.Conclusions:1.The definition of autophagic vacuolar myopathy is more likely to be a group of diseases with similar muscle pathological manifestations.The clinical symptoms mainly show the involvement of various muscle parts of the whole body,especially proximal limb weakness.In some types of muscle damage,the muscle damage outside skeletal muscle may appear earlier or more obvious than the symptoms of skeletal muscle damage.Serum creatine kinase,neuroelectrophysiology,magnetic resonance imaging and other examination methods can provide evidence for diagnosis.Genetic testing and enzyme detection are more meaningful for the diagnosis of some diseases.2.The pathological manifestations of vacuolar autophagic myopathy can be divided into lysosomal storage disease with glycogen storage vacuoles in muscle fiber cells(Pompe disease)and autophagy-vacuolar AVSF with sarcolemmal characteristics.The latter pathological structure is more common and more characteristic,and may be present in almost all AVMs.Most AVSF had multilayer basement membrane along the vacuolar membrane and C5b9 deposition.There are likely to be other disorders with these similar pathological features,which would expand the spectrum of autophagic vacuolar myopathy. |
