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Myopathy, tubular aggregate, 1(TAM1)

MedGen UID:
860163
Concept ID:
C4011726
Disease or Syndrome
Synonym: TAM1
 
Gene (location): STIM1 (11p15.4)
 
Monarch Initiative: MONDO:0024531
OMIM®: 160565

Definition

Tubular aggregates in muscle, first described by Engel (1964), are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They are a nonspecific pathologic finding that may occur in a variety of circumstances, including alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness, and inherited myopathies. Tubular aggregates are derived from the sarcoplasmic reticulum (Salviati et al., 1985) and are believed to represent an adaptive mechanism aimed at regulating an increased intracellular level of calcium in order to prevent the muscle fibers from hypercontraction and necrosis (Martin et al., 1997; Muller et al., 2001). Genetic Heterogeneity of Tubular Aggregate Myopathy See also TAM2 (615883), caused by mutation in the ORAI1 gene (610277) on chromosome 12q24. [from OMIM]

Additional description

From MedlinePlus Genetics
Tubular aggregate myopathy is a disorder that primarily affects the skeletal muscles, which are muscles the body uses for movement. This disorder causes muscle pain, cramping, or weakness that begins in childhood and worsens over time. The muscles of the lower limbs are most often affected, although the upper limbs can also be involved. Affected individuals can have difficulty running, climbing stairs, or getting up from a squatting position. The weakness may also lead to an unusual walking style (gait). Some people with this condition develop joint deformities (contractures) in the arms and legs.

Skeletal muscles are normally made up of two types of fibers, called type I and type II fibers, in approximately equal quantities. Type I fibers, also called slow twitch fibers, are used for long, sustained activity, such as walking long distances. Type II fibers, also known as fast twitch fibers, are used for short bursts of strength, which are needed for activities such as running up stairs or sprinting. In people with tubular aggregate myopathy, type II fibers waste away (atrophy), so affected individuals have mostly type I fibers. In addition, proteins build up abnormally in both type I and type II fibers, forming clumps of tube-like structures called tubular aggregates. Tubular aggregates can occur in other muscle disorders, but they are the primary muscle cell abnormality in tubular aggregate myopathy.  https://medlineplus.gov/genetics/condition/tubular-aggregate-myopathy

Clinical features

From HPO
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Weakness of the intrinsic hand muscles
MedGen UID:
322432
Concept ID:
C1834536
Finding
Hyporeflexia of lower limbs
MedGen UID:
371881
Concept ID:
C1834696
Finding
Reduced intensity of muscle tendon reflexes in the lower limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Joint contracture
MedGen UID:
3228
Concept ID:
C0009918
Anatomical Abnormality
A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Muscle stiffness
MedGen UID:
113151
Concept ID:
C0221170
Sign or Symptom
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Proximal amyotrophy
MedGen UID:
342591
Concept ID:
C1850794
Disease or Syndrome
Amyotrophy (muscular atrophy) affecting the proximal musculature.
Type 1 muscle fiber predominance
MedGen UID:
344274
Concept ID:
C1854387
Finding
An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy).
Type 2 muscle fiber atrophy
MedGen UID:
355249
Concept ID:
C1864580
Pathologic Function
Atrophy (wasting) affecting primary type 2 muscle fibers. This feature in general can only be observed on muscle biopsy.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
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.
Night blindness
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
Inability to see well at night or in poor light.
Abnormal pupil morphology
MedGen UID:
450993
Concept ID:
C0154936
Finding
An abnormality of the pupil.
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.

Professional guidelines

PubMed

de Winter JM, Gineste C, Minardi E, Brocca L, Rossi M, Borsboom T, Beggs AH, Bernard M, Bendahan D, Hwee DT, Malik FI, Pellegrino MA, Bottinelli R, Gondin J, Ottenheijm CAC
Hum Mol Genet 2021 Jun 26;30(14):1305-1320. doi: 10.1093/hmg/ddab112. PMID: 33909041Free PMC Article
Morin G, Biancalana V, Echaniz-Laguna A, Noury JB, Lornage X, Moggio M, Ripolone M, Violano R, Marcorelles P, Maréchal D, Renaud F, Maurage CA, Tard C, Cuisset JM, Laporte J, Böhm J
Hum Mutat 2020 Jan;41(1):17-37. Epub 2019 Sep 15 doi: 10.1002/humu.23899. PMID: 31448844
Naddaf E, Milone M, Kansagra A, Buadi F, Kourelis T
Neurology 2019 Jul 16;93(3):e298-e305. Epub 2019 Jun 5 doi: 10.1212/WNL.0000000000007777. PMID: 31167932

Recent clinical studies

Etiology

Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
D'Amico A, Bertini E
Curr Neurol Neurosci Rep 2008 Jan;8(1):73-9. doi: 10.1007/s11910-008-0012-3. PMID: 18367042
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Sharma MC, Goebel HH
Neurol India 2005 Sep;53(3):273-9. doi: 10.4103/0028-3886.16921. PMID: 16230791
Bruno C, Minetti C
Curr Neurol Neurosci Rep 2004 Jan;4(1):68-73. doi: 10.1007/s11910-004-0015-7. PMID: 14683632

Diagnosis

Younger DS
Handb Clin Neurol 2023;195:533-561. doi: 10.1016/B978-0-323-98818-6.00027-3. PMID: 37562885
Ogasawara M, Nishino I
Neuromuscul Disord 2021 Oct;31(10):968-977. Epub 2021 Sep 17 doi: 10.1016/j.nmd.2021.08.015. PMID: 34627702
Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
Morin G, Biancalana V, Echaniz-Laguna A, Noury JB, Lornage X, Moggio M, Ripolone M, Violano R, Marcorelles P, Maréchal D, Renaud F, Maurage CA, Tard C, Cuisset JM, Laporte J, Böhm J
Hum Mutat 2020 Jan;41(1):17-37. Epub 2019 Sep 15 doi: 10.1002/humu.23899. PMID: 31448844
D'Amico A, Bertini E
Curr Neurol Neurosci Rep 2008 Jan;8(1):73-9. doi: 10.1007/s11910-008-0012-3. PMID: 18367042

Therapy

Shieh PB, Kuntz NL, Dowling JJ, Müller-Felber W, Bönnemann CG, Seferian AM, Servais L, Smith BK, Muntoni F, Blaschek A, Foley AR, Saade DN, Neuhaus S, Alfano LN, Beggs AH, Buj-Bello A, Childers MK, Duong T, Graham RJ, Jain M, Coats J, MacBean V, James ES, Lee J, Mavilio F, Miller W, Varfaj F, Murtagh M, Han C, Noursalehi M, Lawlor MW, Prasad S, Rico S
Lancet Neurol 2023 Dec;22(12):1125-1139. doi: 10.1016/S1474-4422(23)00313-7. PMID: 37977713
van Kleef ESB, Langer D, van Engelen BGM, Ottenheijm CAC, Voermans NC, Doorduin J
J Neuromuscul Dis 2023;10(5):825-834. doi: 10.3233/JND-221665. PMID: 37458044Free PMC Article
Loarce-Martos J, Lilleker JB, Parker M, McHugh N, Chinoy H
Rheumatology (Oxford) 2021 Jul 1;60(7):3398-3403. doi: 10.1093/rheumatology/keaa801. PMID: 33367878
Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F
Nat Rev Neurol 2018 Mar;14(3):151-167. Epub 2018 Feb 2 doi: 10.1038/nrneurol.2017.191. PMID: 29391587
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article

Prognosis

Younger DS
Handb Clin Neurol 2023;195:533-561. doi: 10.1016/B978-0-323-98818-6.00027-3. PMID: 37562885
Bester EG, Kitshoff AM, Botha WJ, Van Wilpe E, Du Plessis L, Williams J
J S Afr Vet Assoc 2022 Jun;93(1):38a-38h. PMID: 35950808
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
Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F
Nat Rev Neurol 2018 Mar;14(3):151-167. Epub 2018 Feb 2 doi: 10.1038/nrneurol.2017.191. PMID: 29391587
Cassandrini D, Trovato R, Rubegni A, Lenzi S, Fiorillo C, Baldacci J, Minetti C, Astrea G, Bruno C, Santorelli FM; Italian Network on Congenital Myopathies
Ital J Pediatr 2017 Nov 15;43(1):101. doi: 10.1186/s13052-017-0419-z. PMID: 29141652Free PMC Article

Clinical prediction guides

Chivet M, McCluskey M, Nicot AS, Brocard J, Beaufils M, Giovannini D, Giannesini B, Poreau B, Brocard J, Humbert S, Saudou F, Fauré J, Marty I
J Gen Physiol 2023 Jan 2;155(1) Epub 2022 Nov 21 doi: 10.1085/jgp.202213103. PMID: 36409218Free PMC Article
Gurgel-Giannetti J, Souza LS, Yamamoto GL, Belisario M, Lazar M, Campos W, Pavanello RCM, Zatz M, Reed U, Zanoteli E, Oliveira AB, Lehtokari VL, Casella EB, Machado-Costa MC, Wallgren-Pettersson C, Laing NG, Nigro V, Vainzof M
Int J Mol Sci 2022 Oct 9;23(19) doi: 10.3390/ijms231911995. PMID: 36233295Free PMC Article
du Fay de Lavallaz J, Prepoudis A, Wendebourg MJ, Kesenheimer E, Kyburz D, Daikeler T, Haaf P, Wanschitz J, Löscher WN, Schreiner B, Katan M, Jung HH, Maurer B, Hammerer-Lercher A, Mayr A, Gualandro DM, Acket A, Puelacher C, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Glarner N, Shrestha S, Manka R, Gawinecka J, Piscuoglio S, Gallon J, Wiedemann S, Sinnreich M, Mueller C; BASEL XII Investigators
Circulation 2022 Jun 14;145(24):1764-1779. Epub 2022 Apr 7 doi: 10.1161/CIRCULATIONAHA.121.058489. PMID: 35389756Free PMC Article
Rudnik-Schöneborn S, Wallgren-Pettersson C
Semin Pediatr Neurol 2019 Apr;29:23-29. Epub 2019 Jan 16 doi: 10.1016/j.spen.2019.01.006. PMID: 31060722
Lacruz RS, Feske S
Ann N Y Acad Sci 2015 Nov;1356(1):45-79. Epub 2015 Oct 15 doi: 10.1111/nyas.12938. PMID: 26469693Free PMC Article

Recent systematic reviews

Middelink M, Voermans NC, van Engelen BGM, Janssen MCH, Groothuis JT, Knuijt S, Zweers-van Essen H
J Neuromuscul Dis 2023;10(5):777-785. doi: 10.3233/JND-230014. PMID: 37483025Free PMC Article
Christophers B, Lopez MA, Gupta VA, Vogel H, Baylies M
J Child Neurol 2022 Jun;37(7):652-663. Epub 2022 Jun 7 doi: 10.1177/08830738221096316. PMID: 36960434Free PMC Article

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