背景:具有过度自噬的X连锁肌病(XMEA)的特征是具有肌膜特征的自噬液泡。VMA21突变导致溶酶体酸化不足,导致进行性近端无力,在20岁之前发病,到中年时失去下床活动。
方法:我们描述了一名50岁后下肢缓慢进行性近端无力发作的患者,该患者在71岁时在手杖的帮助下保持步行。
结果:66岁时的肌肉活检显示复杂的肌纤维分裂,内化毛细血管,和自噬性空泡性肌病的空泡改变。液泡对肌膜蛋白染色阳性,LAMP2和补体C5b-9。超微结构评估进一步显示基底层重复和广泛的自噬体挤出。Sanger测序鉴定了VMA21中已知的病理剪接位点突变(c.164-7T>G)。
结论:该病例扩展了XMEA的临床表型,并建议在评估患有LAMP2阳性自噬空泡性肌病的男性时考虑VMA21测序。
BACKGROUND: X-linked myopathy with excessive autophagy (XMEA) is characterized by autophagic vacuoles with sarcolemmal features. Mutations in VMA21 result in insufficient lysosome acidification, causing progressive proximal weakness with onset before age 20 years and loss of ambulation by middle age.
METHODS: We describe a patient with onset of slowly progressive proximal weakness of the lower limbs after age 50, who maintains ambulation with the assistance of a cane at age 71.
RESULTS: Muscle biopsy at age 66 showed complex muscle fiber splitting, internalized capillaries, and vacuolar changes characteristic of autophagic vacuolar myopathy. Vacuoles stained positive for sarcolemmal proteins, LAMP2, and complement C5b-9. Ultrastructural evaluation further revealed basal lamina reduplication and extensive autophagosome extrusion. Sanger sequencing identified a known pathologic splice site mutation in VMA21 (c.164-7T>G).
CONCLUSIONS: This case expands the clinical phenotype of XMEA and suggests VMA21 sequencing be considered in evaluating men with LAMP2-positive autophagic vacuolar myopathy.