Late adult-onset of X-linked myopathy with excessive autophagy.
BACKGROUND
X-linked myopathy with excessive autophagy (XMEA) is characterized by autophagic vacuoles with sarcolemmal features. Mutations in VMA21 result in insufficient lysosome acidification, causing progressive proximal weakness with onset before age 20 years and loss of ambulation by middle age.


METHODS
We describe a patient with onset of slowly progressive proximal weakness of the lower limbs after age 50, who maintains ambulation with the assistance of a cane at age 71.


RESULTS
Muscle biopsy at age 66 showed complex muscle fiber splitting, internalized capillaries, and vacuolar changes characteristic of autophagic vacuolar myopathy. Vacuoles stained positive for sarcolemmal proteins, LAMP2, and complement C5b-9. Ultrastructural evaluation further revealed basal lamina reduplication and extensive autophagosome extrusion. Sanger sequencing identified a known pathologic splice site mutation in VMA21 (c.164-7T>G).


CONCLUSIONS
This case expands the clinical phenotype of XMEA and suggests VMA21 sequencing be considered in evaluating men with LAMP2-positive autophagic vacuolar myopathy.
Department of Pathology, University of Iowa Carver College of Medicine, Room 5239B, RCP, 200 Hawkins Drive, Iowa City, Iowa, 52242, USA.
Cameron D
CD
Crockett
Alessandra
A
Ruggieri
Meena
M
Gujrati
Christopher M
CM
Zallek
Nivetha
N
Ramachandran
Berge A
BA
Minassian
Steven A
SA
Moore
D000368:Aged; D001343:Autophagy / Q000235:genetics* / Q000502:physiology; D001706:Biopsy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004576:Electromyography; D005091:Exons / Q000235:genetics; D005455:Fluorescent Antibody Technique; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007438:Introns / Q000235:genetics; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018908:Muscle Weakness / Q000209:etiology / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
C540401:VMA21 protein, human; D025262:Vacuolar Proton-Translocating ATPases
VMA21; X-linked myopathy with excessive autophagy; autophagic vacuolar myopathy; autophagic vacuoles with sarcolemmal features; progressive proximal muscle weakness