Abstract：
OBJECTIVE: X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA.
METHODS: We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases.
RESULTS: Eighteen males had genetically confirmed XMEA in France, carrying four different VMA21 variants. Mean age at disease onset was 9.4 ± 9.9 (range 1-40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n = 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39-48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%).
CONCLUSIONS: XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype-phenotype correlations will help design future clinical trials.
METHODS: We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases.
RESULTS: Eighteen males had genetically confirmed XMEA in France, carrying four different VMA21 variants. Mean age at disease onset was 9.4 ± 9.9 (range 1-40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n = 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39-48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%).
CONCLUSIONS: XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype-phenotype correlations will help design future clinical trials.
摘要：
目的：与VMA21基因相关的过度自噬（XMEA）的X连锁肌病导致自噬失败，进行性空泡化和骨骼肌萎缩。目前对这种罕见疾病的了解有限。我们的目标是定义临床，放射学,和XMEA的自然史。
方法：我们进行了一项回顾性研究，收集临床资料，遗传,肌肉成像,法国对XMEA患者的活检数据进行了随访，并对其他病例进行了文献回顾。
结果：18名男性在法国通过基因证实了XMEA，携带四种不同的VMA21变体。发病时的平均年龄为9.4±9.9（范围1-40）岁。在14/18患者中（77.8％），发病发生在儿童期（<15岁）；然而在四名患者中，这种疾病始于成年。患者有大腿前和内侧室肌无力，远端挛缩（56.3%），在肌肉组织病理学上，CK水平升高（1287.9±757.8U/l）和具有肌膜特征的自噬液泡。肌肉MRI（n=10）显示下肢肌肉受累的特征性模式。在11名患者中，平均随访时间为10.6±9.8年,其中6项显示疾病进展.Brooke功能结局的平均变化为0.5±1.2分，Vignos评分为2.2±2.5分，7/16患者（43.8％）需要助行器，3/16（18.8％）为轮椅（中位年龄为40岁，范围39-48）。变异c.164-7T>G与症状发作较晚有关。呼吸功能不全是常见的（57.1％），但心脏受累很少（12.5％）。
结论：XMEA有不同的发病年龄，而是一个典型的临床，组织病理学,和肌肉成像演示，指导诊断。虽然缓慢，运动障碍随着时间的推移而发展，和相关的基因型-表型相关性将有助于设计未来的临床试验。
方法：我们进行了一项回顾性研究，收集临床资料，遗传,肌肉成像,法国对XMEA患者的活检数据进行了随访，并对其他病例进行了文献回顾。
结果：18名男性在法国通过基因证实了XMEA，携带四种不同的VMA21变体。发病时的平均年龄为9.4±9.9（范围1-40）岁。在14/18患者中（77.8％），发病发生在儿童期（<15岁）；然而在四名患者中，这种疾病始于成年。患者有大腿前和内侧室肌无力，远端挛缩（56.3%），在肌肉组织病理学上，CK水平升高（1287.9±757.8U/l）和具有肌膜特征的自噬液泡。肌肉MRI（n=10）显示下肢肌肉受累的特征性模式。在11名患者中，平均随访时间为10.6±9.8年,其中6项显示疾病进展.Brooke功能结局的平均变化为0.5±1.2分，Vignos评分为2.2±2.5分，7/16患者（43.8％）需要助行器，3/16（18.8％）为轮椅（中位年龄为40岁，范围39-48）。变异c.164-7T>G与症状发作较晚有关。呼吸功能不全是常见的（57.1％），但心脏受累很少（12.5％）。
结论：XMEA有不同的发病年龄，而是一个典型的临床，组织病理学,和肌肉成像演示，指导诊断。虽然缓慢，运动障碍随着时间的推移而发展，和相关的基因型-表型相关性将有助于设计未来的临床试验。
