Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder caused by bi-allelic pathogenic variants in the gene MCOLN1. This encodes for mucolipin-1 (ML1), an endo-lysosomal transmembrane Ca++ channel involved in vesicular trafficking. Although experimental models suggest that defects in mucolipin-1 can cause muscular dystrophy, putatively due to defective lysosomal-mediated sarcolemma repair, the role of mucolipin-1 in human muscle is still poorly deciphered. Elevation of creatine kinase (CK) had been reported in a few cases in the past but comprehensive descriptions of muscle pathology are lacking. Here we report a 7-year-old boy who underwent muscle biopsy due to persistently elevated CK levels (780-15,000 UI/L). Muscle pathology revealed features of a lysosomal storage myopathy with mild regenerative changes. Next generation sequencing confirmed homozygous nonsense variants in MCOLN1. This is a comprehensive pathological description of ML1-related myopathy, supporting the role of mucolipin-1 in muscle homoeostasis.

中文翻译：

---

持续升高的 CK 和溶酶体贮积肌病与粘脂素 1 缺陷相关

粘脂贮积症 IV 型是一种罕见的常染色体隐性溶酶体贮积症，由基因 MCOLN1 中的双等位基因致病变异引起。这编码 mucolipin-1 (ML1)，一种参与囊泡运输的内溶酶体跨膜 Ca++ 通道。尽管实验模型表明 mucolipin-1 中的缺陷可导致肌营养不良症，推测是由于溶酶体介导的肌膜修复缺陷，但 mucolipin-1 在人类肌肉中的作用仍不清楚。过去曾在少数病例中报道过肌酸激酶 (CK) 升高，但缺乏对肌肉病理学的全面描述。在这里，我们报告了一名 7 岁男孩，由于 CK 水平持续升高 (780-15,000 UI/L)，他接受了肌肉活检。肌肉病理显示溶酶体贮积性肌病的特征，具有轻度再生性改变。下一代测序证实了 MCOLN1 中的纯合无义变异。这是 ML1 相关肌病的综合病理描述，支持 mucolipin-1 在肌肉稳态中的作用。