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Myopathy, autophagic vacuolar, infantile-onset

MedGen UID:
419364
•Concept ID:
C2931230
•
Disease or Syndrome
Synonyms: Autophagic vacuolar myopathy; Myopathy, Autophagic Vacuolar, Infantile-Onset; Vacuolar myopathy
 
Monarch Initiative: MONDO:0012286
OMIM®: 609500

Definition

Infantile-onset autophagic vacuolar myopathy is characterized by increased cardiac and skeletal muscle glycogen with normal acid maltase (GAA; 606800). Skeletal muscle biopsy shows characteristic intracytoplasmic vacuoles that stain for sarcolemmal proteins and complement proteins. Similar pathologic findings are seen in Danon disease (300257), caused by mutation in the LAMP2 gene (309060) on chromosome Xq24, and X-linked myopathy with excessive autophagy (XMEA; 310440), which has been mapped to Xq28. [from OMIM]

Clinical features

From HPO
Hypertrophic cardiomyopathy
MedGen UID:
2881
•Concept ID:
C0007194
•
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
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Global developmental delay
MedGen UID:
107838
•Concept ID:
C0557874
•
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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Myopathy
MedGen UID:
10135
•Concept ID:
C0026848
•
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
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Autophagic vacuoles
MedGen UID:
107466
•Concept ID:
C0544966
•
Finding
The lysosomal-vacuolar pathway has a role in the controlled intracellular digestion of macromolecules such as protein complexes and organelles. This feature refers to the presence of an abnormally increased number of autophagic vacuoles in muscle tissue.
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Neonatal hypotonia
MedGen UID:
412209
•Concept ID:
C2267233
•
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
See: Feature record | Search on this feature
Elevated circulating creatine kinase concentration
MedGen UID:
69128
•Concept ID:
C0241005
•
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
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Professional guidelines

PubMed

International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review.
Hong KN, Eshraghian EA, Arad M, Argirò A, Brambatti M, Bui Q, Caspi O, de Frutos F, Greenberg B, Ho CY, Kaski JP, Olivotto I, Taylor MRG, Yesso A, Garcia-Pavia P, Adler ED
J Am Coll Cardiol 2023 Oct 17;82(16):1628-1647. doi: 10.1016/j.jacc.2023.08.014. PMID: 37821174
Novel autophagic vacuolar myopathies: Phenotype and genotype features.
Napolitano F, Terracciano C, Bruno G, De Blasiis P, Lombardi L, Gialluisi A, Gianfrancesco F, De Giovanni D, Tummolo A, Di Iorio G, Limongelli G, Esposito T, Melone MAB, Sampaolo S
Neuropathol Appl Neurobiol 2021 Aug;47(5):664-678. Epub 2021 Feb 1 doi: 10.1111/nan.12690. PMID: 33393119
Differential diagnosis of vacuolar myopathies in the NGS era.
Mair D, Biskup S, Kress W, Abicht A, Brück W, Zechel S, Knop KC, Koenig FB, Tey S, Nikolin S, Eggermann K, Kurth I, Ferbert A, Weis J
Brain Pathol 2020 Sep;30(5):877-896. Epub 2020 Jun 15 doi: 10.1111/bpa.12864. PMID: 32419263Free PMC Article

Recent clinical studies

Etiology

Novel autophagic vacuolar myopathies: Phenotype and genotype features.
Napolitano F, Terracciano C, Bruno G, De Blasiis P, Lombardi L, Gialluisi A, Gianfrancesco F, De Giovanni D, Tummolo A, Di Iorio G, Limongelli G, Esposito T, Melone MAB, Sampaolo S
Neuropathol Appl Neurobiol 2021 Aug;47(5):664-678. Epub 2021 Feb 1 doi: 10.1111/nan.12690. PMID: 33393119
X-linked myopathy with excessive autophagy: a failure of self-eating.
Dowling JJ, Moore SA, Kalimo H, Minassian BA
Acta Neuropathol 2015 Mar;129(3):383-90. Epub 2015 Feb 3 doi: 10.1007/s00401-015-1393-4. PMID: 25644398
Autophagic vacuolar pathology in desminopathies.
Weihl CC, Iyadurai S, Baloh RH, Pittman SK, Schmidt RE, Lopate G, Pestronk A, Harms MB
Neuromuscul Disord 2015 Mar;25(3):199-206. Epub 2014 Dec 12 doi: 10.1016/j.nmd.2014.12.002. PMID: 25557463Free PMC Article
Autophagic vacuolar myopathy.
Nishino I
Semin Pediatr Neurol 2006 Jun;13(2):90-5. doi: 10.1016/j.spen.2006.06.004. PMID: 17027858
Drug-induced myopathies.
Le Quintrec JS, Le Quintrec JL
Baillieres Clin Rheumatol 1991 Apr;5(1):21-38. doi: 10.1016/s0950-3579(05)80294-8. PMID: 2070426

Diagnosis

Novel autophagic vacuolar myopathies: Phenotype and genotype features.
Napolitano F, Terracciano C, Bruno G, De Blasiis P, Lombardi L, Gialluisi A, Gianfrancesco F, De Giovanni D, Tummolo A, Di Iorio G, Limongelli G, Esposito T, Melone MAB, Sampaolo S
Neuropathol Appl Neurobiol 2021 Aug;47(5):664-678. Epub 2021 Feb 1 doi: 10.1111/nan.12690. PMID: 33393119
Review: Danon disease: Review of natural history and recent advances.
Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C
Neuropathol Appl Neurobiol 2020 Jun;46(4):303-322. Epub 2019 Nov 25 doi: 10.1111/nan.12587. PMID: 31698507
Myopathy and scleromyxedema.
Soulages A, Tang HM, Pham-Ledard A, Négrier-Leibreich ML, Cosnard A, Duval F, Solé G, Carla L, Le Masson G, Mathis S
J Neurol 2019 Aug;266(8):2051-2059. Epub 2019 May 21 doi: 10.1007/s00415-019-09379-w. PMID: 31115676
Danon disease: Gender differences in presentation and outcomes.
Brambatti M, Caspi O, Maolo A, Koshi E, Greenberg B, Taylor MRG, Adler ED
Int J Cardiol 2019 Jul 1;286:92-98. Epub 2019 Feb 16 doi: 10.1016/j.ijcard.2019.01.020. PMID: 30857840
Diagnosis of Pompe disease: muscle biopsy vs blood-based assays.
Vissing J, Lukacs Z, Straub V
JAMA Neurol 2013 Jul;70(7):923-7. doi: 10.1001/2013.jamaneurol.486. PMID: 23649721

Therapy

Teaching NeuroImages: Colchicine-induced vacuolar myopathy.
Sista SR, Nyce MQ, Bach SE, Blume GM
Neurology 2019 Dec 10;93(24):e2306-e2307. doi: 10.1212/WNL.0000000000008636. PMID: 31819001
Myopathy and scleromyxedema.
Soulages A, Tang HM, Pham-Ledard A, Négrier-Leibreich ML, Cosnard A, Duval F, Solé G, Carla L, Le Masson G, Mathis S
J Neurol 2019 Aug;266(8):2051-2059. Epub 2019 May 21 doi: 10.1007/s00415-019-09379-w. PMID: 31115676
Neuromuscular transmission defects in myopathies: Rare but worth searching for.
Elahi B, Laughlin RS, Litchy WJ, Milone M, Liewluck T
Muscle Nerve 2019 Apr;59(4):475-478. Epub 2019 Jan 6 doi: 10.1002/mus.26393. PMID: 30536954
Hydroxychloroquine-induced autophagic vacuolar myopathy with mitochondrial abnormalities.
Khosa S, Khanlou N, Khosa GS, Mishra SK
Neuropathology 2018 Dec;38(6):646-652. Epub 2018 Nov 8 doi: 10.1111/neup.12520. PMID: 30411412
Severe hydroxychloroquine myopathy.
Abdel-Hamid H, Oddis CV, Lacomis D
Muscle Nerve 2008 Sep;38(3):1206-10. doi: 10.1002/mus.21091. PMID: 18720511

Prognosis

X-linked Myopathy with Excessive Autophagy - A Rare Cause of Vacuolar Myopathy in Children.
Rajeshwari M, Dhiman N, Chakrabarty B, Gulati S, Shamim U, Faruq M, Suri V, Sharma MC
Neurol India 2022 Jul-Aug;70(4):1643-1648. doi: 10.4103/0028-3886.355110. PMID: 36076674
Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation.
Jiang K, Zheng Y, Lin J, Wu X, Yu Y, Zhu M, Fang X, Zhou M, Li X, Hong D
Brain Behav 2022 Feb;12(2):e2469. Epub 2022 Jan 3 doi: 10.1002/brb3.2469. PMID: 34978387Free PMC Article
Review: Danon disease: Review of natural history and recent advances.
Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C
Neuropathol Appl Neurobiol 2020 Jun;46(4):303-322. Epub 2019 Nov 25 doi: 10.1111/nan.12587. PMID: 31698507
Muscle pathology in Vici syndrome-A case study with a novel mutation in EPG5 and a summary of the literature.
Hedberg-Oldfors C, Darin N, Oldfors A
Neuromuscul Disord 2017 Aug;27(8):771-776. Epub 2017 May 8 doi: 10.1016/j.nmd.2017.05.005. PMID: 28624465
A novel mutation af Cln3 associated with delayed-classic juvenile ceroid lipofuscinois and autophagic vacuolar myopathy.
Licchetta L, Bisulli F, Fietz M, Valentino ML, Morbin M, Mostacci B, Oliver KL, Berkovic SF, Tinuper P
Eur J Med Genet 2015 Oct;58(10):540-4. Epub 2015 Sep 7 doi: 10.1016/j.ejmg.2015.09.002. PMID: 26360874

Clinical prediction guides

C-terminal frameshift variant of TDP-43 with pronounced aggregation-propensity causes rimmed vacuole myopathy but not ALS/FTD.
Ervilha Pereira P, Schuermans N, Meylemans A, LeBlanc P, Versluys L, Copley KE, Rubien JD, Altheimer C, Peetermans M, Debackere E, Vanakker O, Janssens S, Baets J, Verhoeven K, Lammens M, Symoens S, De Paepe B, Barmada SJ, Shorter J, De Bleecker JL, Bogaert E, Dermaut B
Acta Neuropathol 2023 Jun;145(6):793-814. Epub 2023 Mar 31 doi: 10.1007/s00401-023-02565-1. PMID: 37000196Free PMC Article
Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation.
Jiang K, Zheng Y, Lin J, Wu X, Yu Y, Zhu M, Fang X, Zhou M, Li X, Hong D
Brain Behav 2022 Feb;12(2):e2469. Epub 2022 Jan 3 doi: 10.1002/brb3.2469. PMID: 34978387Free PMC Article
Autophagy Defects in Skeletal Myopathies.
Margeta M
Annu Rev Pathol 2020 Jan 24;15:261-285. Epub 2019 Oct 8 doi: 10.1146/annurev-pathmechdis-012419-032618. PMID: 31594457
Myopathy and scleromyxedema.
Soulages A, Tang HM, Pham-Ledard A, Négrier-Leibreich ML, Cosnard A, Duval F, Solé G, Carla L, Le Masson G, Mathis S
J Neurol 2019 Aug;266(8):2051-2059. Epub 2019 May 21 doi: 10.1007/s00415-019-09379-w. PMID: 31115676
Clinical and histologic ocular findings in pompe disease.
Yanovitch TL, Banugaria SG, Proia AD, Kishnani PS
J Pediatr Ophthalmol Strabismus 2010 Jan-Feb;47(1):34-40. Epub 2010 Jan 21 doi: 10.3928/01913913-20100106-08. PMID: 20128552

Recent systematic reviews

Autopsy findings in late-onset Pompe disease: a case report and systematic review of the literature.
Hobson-Webb LD, Proia AD, Thurberg BL, Banugaria S, Prater SN, Kishnani PS
Mol Genet Metab 2012 Aug;106(4):462-9. Epub 2012 May 18 doi: 10.1016/j.ymgme.2012.05.007. PMID: 22664150
Clinical and histologic ocular findings in pompe disease.
Yanovitch TL, Banugaria SG, Proia AD, Kishnani PS
J Pediatr Ophthalmol Strabismus 2010 Jan-Feb;47(1):34-40. Epub 2010 Jan 21 doi: 10.3928/01913913-20100106-08. PMID: 20128552

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