Persistently elevated CK and lysosomal storage myopathy associated with mucolipin 1 defects
| Autor: | Stephanie Grunewald, Anna Sarkozy, Alberto A. Zambon, Alexandra Lemaigre, Emma Clement, Francesco Muntoni, Rahul Phadke, Caroline Sewry |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty 03 medical and health sciences 0302 clinical medicine Lysosome medicine Muscular dystrophy Myopathy Genetics (clinical) MCOLN1 Sarcolemma Muscle biopsy biology medicine.diagnostic_test business.industry medicine.disease 030104 developmental biology medicine.anatomical_structure Neurology Pediatrics Perinatology and Child Health biology.protein Creatine kinase Neurology (clinical) Mucolipidosis type IV medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders. 31:212-217 |
| ISSN: | 0960-8966 |
| DOI: | 10.1016/j.nmd.2020.12.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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