X-linked Myopathy with Excessive Autophagy - A Rare Cause of Vacuolar Myopathy in Children.

X-linked myopathy with excessive autophagy (XMEA) is a rare, recently characterized type of autophagic vacuolar myopathy caused by mutations in the VMA21 gene. It is characterized by slowly progressive weakness restricted to proximal limb muscles and generally has a favorable outcome. The characteristic histological and ultrastructural features distinguish this entity from other mimics, notably Danon disease. XMEA is an under recognized disease and should be considered in the differentials of slowly progressive myopathy in children. Awareness of this rare entity is also important for the pathologists in order to distinguish it from other causes of vacuolar myopathy in view of its favourable prognosis. We report the first genetically confirmed case of XMEA from India in an 8-year-old boy which was diagnosed based on the characteristic light microscopic and ultrastructural findings on muscle biopsy and subsequently confirmed by mutation analysis. The differential diagnostic considerations are also discussed.

[1]  S. Chandra,et al.  X-Linked Myopathy with Excessive Autophagy; A Case Report , 2019, Neurology India.

[2]  H. Goebel,et al.  Autophagic vacuolar myopathy is a common feature of CLN3 disease , 2018, Annals of clinical and translational neurology.

[3]  S. Mercier,et al.  Muscle magnetic resonance imaging abnormalities in X‐linked myopathy with excessive autophagy , 2015, Muscle & nerve.

[4]  I. Nishino,et al.  Congenital autophagic vacuolar myopathy is allelic to X-linked myopathy with excessive autophagy , 2015, Neurology.

[5]  A. Pestronk,et al.  Autophagic vacuolar pathology in desminopathies , 2015, Neuromuscular Disorders.

[6]  E. Haan,et al.  Non-coding VMA21 deletions cause X-linked Myopathy with Excessive Autophagy , 2015, Neuromuscular Disorders.

[7]  J. Dowling,et al.  X-linked myopathy with excessive autophagy: a failure of self-eating , 2015, Acta Neuropathologica.

[8]  Christopher M. Zallek,et al.  Late adult‐onset of X‐linked myopathy with excessive autophagy , 2014, Muscle & nerve.

[9]  I. Nonaka,et al.  Elevated urinary β2 microglobulin in the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy , 2013, Neuromuscular Disorders.

[10]  J. Rilstone,et al.  VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy , 2013, Acta Neuropathologica.

[11]  I. Nishino,et al.  Autophagy in Lysosomal Myopathies , 2012, Brain pathology.

[12]  M. Vatta,et al.  Danon disease as a cause of autophagic vacuolar myopathy. , 2007, Congenital Heart Disease.

[13]  I. Nishino.  Autophagic vacuolar myopathy. , 2006, Seminars in pediatric neurology.

[14]  N. Murase,et al.  A new congenital form of X-linked autophagic vacuolar myopathy , 2005, Neurology.

[15]  I. Nonaka,et al.  Autophagic Vacuoles with Sarcolemmal Features Delineate Danon Disease and Related Myopathies , 2005, Journal of neuropathology and experimental neurology.

[16]  I. Nonaka,et al.  A novel form of autophagic vacuolar myopathy with late-onset and multiorgan involvement , 2003, Neurology.

[17]  B. Falck,et al.  Electrophysiological findings in X‐linked myopathy with excessive autophagy , 2002, Annals of neurology.

[18]  I. Nonaka,et al.  Infantile autophagic vacuolar myopathy is distinct from Danon disease , 2001, Neurology.

[19]  D. Figarella-Branger,et al.  X-linked myopathy with excessive autophagy: a clinicopathological study of five new families , 2001, Neuromuscular Disorders.

[20]  M. Villanova,et al.  X‐linked vacuolated myopathy: Complement membrane attack complex on surface membrane of injured muscle fibers , 1995, Annals of neurology.

[21]  P. Dean,et al.  X‐Linked myopathy with excessive autophagy: A new hereditary muscle disease , 1988, Annals of neurology.