VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy

@article{Ramachandran2012VMA21DP,
  title={VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy},
  author={Nivetha Ramachandran and Iulia Munteanu and Peixiang Wang and Alessandra Ruggieri and Jennifer J. Rilstone and Nyrie Israelian and Taline Naranian and Paul Paroutis and Ray Guo and Z P Ren and Ichizo Nishino and Brigitte Chabrol and Jean François Pellissier and Carlo Minetti and Bjarne Udd and Michel Gustave Jules Fardeau and Chetankumar S. Tailor and Don J. Mahuran and John T. Kissel and Hannu O. Kalimo and Nicolas L{\'e}vy and Morris Frank Manolson and Cameron A. Ackerley and Berge A. Minassian},
  journal={Acta Neuropathologica},
  year={2012},
  volume={125},
  pages={439-457}
}
X-linked Myopathy with Excessive Autophagy (XMEA) is a childhood onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p, VMA21 is an essential assembly chaperone of the vacuolar ATPase (V-ATPase), the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH which reduces lysosomal… 
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Given the vital role of V-ATPases in all cells, absence of manifest disease outside muscle is surprising and possibly, extramuscular pathology is actually present but subclinical.
No cardiomyopathy in X-linked myopathy with excessive autophagy
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