Holton J L, Beesley C, Jackson M, Venner K, Bhardwaj N, Winchester B, Al-Memar A
Department of Molecular Neuroscience and Division of Neuropathology, Institute of Neurology, University College London, London, UK.
Neuropathol Appl Neurobiol. 2006 Jun;32(3):253-9. doi: 10.1111/j.1365-2990.2006.00691.x.
Hereditary autophagic vacuolar myopathy (AVM) may occur in several diseases including the rimmed vacuolar myopathies, acid maltase deficiency, Danon disease, infantile autophagic vacuolar myopathy and X-linked myopathy with excessive autophagy (XMEA). In the latter three conditions the vacuoles are lined by membranes with sarcolemmal features. We present two unusual cases of autophagic vacuolar myopathy in twin girls born at term with no family history of neurological disease. After initial normal developmental milestones they developed progressive leg weakness and wasting with contractures from the age of 12 years. Investigations showed raised CK, normal female karyotype, normal acid maltase activity, normal nerve conduction and myopathic EMG features. Frozen sections of skeletal muscle were stained using routine tinctorial and histochemical methods. Immunohistochemical staining for spectrin, merosin, dystrophin, complement membrane attack complex and sarcoglycans was performed and ultrastructural examination undertaken. Direct sequence analysis of the lamp-2 gene using genomic DNA extracted from lymphocytes was performed. Histological analysis of the muscle biopsies demonstrated myofibres with vacuoles lacking glycogen and lipid many of which were delineated using immunohistochemistry for merosin, dystrophin and sarcoglycans. Ultrastructural examination showed duplication of the myofibre basal lamina with associated autophagic material. Vacuoles within myofibres were either membrane bound containing autophagic material or lined by plasma membrane and basal lamina. Intermyofibrillar glycogen was increased. Sequence analysis of the coding region and intron/exon boundaries of the lamp-2 gene was normal. This is the first report of female cases of AVM with sarcolemmal features. We suggest that these patients may represent manifesting carriers of XMEA, or alternatively, a new form of disease with a similar phenotype having autosomal recessive inheritance.
遗传性自噬性空泡性肌病（AVM）可能出现在多种疾病中，包括镶边空泡性肌病、酸性麦芽糖酶缺乏症、Danon病、婴儿型自噬性空泡性肌病以及伴有过度自噬的X连锁肌病（XMEA）。在后三种情况下，空泡由具有肌膜特征的膜所包绕。我们报告了两例非同寻常的自噬性空泡性肌病病例，为足月出生的双胞胎女孩，她们没有神经疾病家族史。在最初达到正常发育里程碑后，她们从12岁起逐渐出现进行性腿部无力和萎缩，并伴有挛缩。检查显示肌酸激酶升高、女性核型正常、酸性麦芽糖酶活性正常、神经传导正常以及肌病性肌电图特征。使用常规染色和组织化学方法对骨骼肌冰冻切片进行染色。进行了血影蛋白、merosin、抗肌萎缩蛋白、补体膜攻击复合物和肌聚糖的免疫组织化学染色，并进行了超微结构检查。使用从淋巴细胞中提取的基因组DNA对lamp - 2基因进行直接序列分析。肌肉活检的组织学分析显示肌纤维有空泡，缺乏糖原和脂质，其中许多通过merosin、抗肌萎缩蛋白和肌聚糖的免疫组织化学得以勾勒。超微结构检查显示肌纤维基底膜重复并伴有相关自噬物质。肌纤维内的空泡要么被含有自噬物质的膜所包裹，要么由质膜和基底膜包绕。肌原纤维间糖原增加。lamp - 2基因编码区及内含子/外显子边界的序列分析正常。这是首例具有肌膜特征的女性AVM病例报告。我们认为这些患者可能代表XMEA的显性携带者，或者是具有相似表型的常染色体隐性遗传新疾病形式。
