Congenital autophagic vacuolar myopathy is allelic to X-linked myopathy with excessive autophagy

X-linked myopathy with excessive autophagy (XMEA) is characterized by weakness and wasting primarily of the proximal muscles of the lower extremities. Onset is usually after age 5 and progression is extremely slow with ambulation maintained well into the 50s. The heart, CNS, peripheral nervous system, and other organs are clinically spared. Pathology reveals large autophagic vacuoles enclosing incompletely degraded cytoplasmic components, which translocate to the myofiber surface and extrude their contents, forming a field of cell debris between multiplied layers of basal lamina. XMEA is caused by mutations of the VMA21 gene, which reduce, but do not eliminate, expression of the chief assembly chaperone (VMA21) of the main proton pump (V-ATPase [vacuolar-type H⁺–adenosine triphosphatase]) of all mammalian cells.

Neurology 2015