National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Tubular aggregate myopathy


Other Names:
Myopathy, tubular aggregate
Categories:
This disease is grouped under:
Tubular aggregate myopathy is a disorder that affects the skeletal muscles. Signs and symptoms typically begin in childhood and worsen over time. The leg muscles are most often affected, but the arm muscles may also be involved.[1] Symptoms include muscle pain, cramping, weakness or stiffness; and exercise-induced muscle fatigue.[1][2][3] Affected individuals may have an unusual walking style (gait) or difficulty running, climbing stairs, or getting up from a squatting position. Some individuals develop contractures.[1] This condition may be caused by mutations in the STIM1 or ORAI1 genes.[4][5] It is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has also been reported.[1]
Last updated: 12/27/2016
The signs and symptoms of tubular aggregate myopathy (TAM) can vary from person to person. Symptoms typically begin in childhood or adolescence and worsen over time.[1][4] However, onset in adulthood has been reported.[4] The leg muscles are most often affected, but the arm muscles may also be involved.[1] The facial muscles are usually not affected. Symptoms include muscle pain, cramping, weakness or stiffness; and exercise-induced muscle fatigue.[1][2][3] Affected individuals may have an unusual walking style (gait); difficulty running, climbing stairs, or getting up from a squatting position; and frequent falls. Some individuals develop contractures.[1][4]
Last updated: 12/27/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 36 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
EMG: myopathic abnormalities 0003458
Fatiguable weakness of proximal limb muscles 0030200
Muscle fiber tubular inclusions 0100301
Muscle spasm 0003394
Myalgia
Muscle ache
Muscle pain
[ more ] 		0003326
30%-79% of people have these symptoms
Centrally nucleated skeletal muscle fibers 0003687
Increased variability in muscle fiber diameter 0003557
5%-29% of people have these symptoms
Abnormal pupil morphology
Abnormality of the pupil
Pupillary abnormalities
Pupillary abnormality
[ more ] 		0000615
External ophthalmoplegia
Paralysis or weakness of muscles within or surrounding outer part of eye
0000544
Flexion contracture
Flexed joint that cannot be straightened
0001371
Nyctalopia
Night blindness
Night-blindness
Poor night vision
[ more ] 		0000662
Respiratory insufficiency
Respiratory impairment
0002093
Type 2 muscle fiber atrophy 0003554
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Areflexia of lower limbs 0002522
Autosomal dominant inheritance 0000006
Difficulty running 0009046
Easy fatigability 0003388
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase
[ more ] 		0003236
Exercise-induced myalgia
Exercise-induced muscle pain
Muscle pain on exercise
Muscle pain with exercise
Muscle pain, exercise-induced
[ more ] 		0003738
Falls 0002527
Foot dorsiflexor weakness
Foot drop
0009027
Frequent falls 0002359
Generalized muscle weakness 0003324
Hypocalcemia
Low blood calcium levels
0002901
Hyporeflexia of lower limbs 0002600
Miosis
Constricted pupils
Pupillary constriction
[ more ] 		0000616
Muscle stiffness 0003552
Myopathy
Muscle tissue disease
0003198
Neck muscle weakness
Floppy neck
0000467
Proximal amyotrophy
Wasting of muscles near the body
0007126
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Slow progression
Signs and symptoms worsen slowly with time
0003677
Spinal rigidity
Reduced spine movement
0003306
Variable expressivity 0003828
Weakness of the intrinsic hand muscles 0009005
Showing of 36 |
Last updated: 7/1/2020
Tubular aggregate myopathy (TAM) may be caused by mutations in the STIM1 or ORAI1 genes.[4][5] The STIM1 gene gives the body instructions to make a protein involved in controlling when calcium ions enter cells. The protein recognizes low ion levels and stimulates the flow of ions into the cell, which amongst other things, stimulates muscle tensing. STIM1 gene mutations that cause TAM lead to the STIM1 protein always being "active," so it is continuously stimulating the entry of calcium ions regardless of ion levels.[1] The protein encoded by the ORAI1 gene is part of a calcium channel on the cell membrane, which is activated by the STIM1 protein when calcium stores are low.[6] Exactly how mutations in these genes lead to the specific symptoms of TAM is still being studied.
Last updated: 12/27/2016
Tubular aggregate myopathy (TAM) is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has also been reported.[1][7][8]

Autosomal dominant inheritance means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of the condition. In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation. Mutations in the STIM1 and ORAI1 genes have been shown to cause autosomal dominant TAM.[4][5]

Autosomal recessive inheritance means that to be affected, a person must have a  mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% chance to be affected
  • 50% chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not a carrier
To our knowledge, the gene, or genes, responsible for autosomal recessive TAM have not yet been identified.

People with personal questions about the genetic cause and inheritance of this condition are encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:
  • thoroughly evaluating the family history
  • addressing questions and concerns
  • assessing recurrence risks
  • facilitating genetic testing if desired
Last updated: 12/28/2016
Currently, the diagnosis of tubular aggregate myopathy (TAM) is made by identifying tubular aggregates in a muscle biopsy (the "hallmark" of TAM).[9] Tubular aggregates are clumps of tube-like structures formed by the abnormal build-up of proteins.[1] Other tests that may be used to support or rule out the diagnosis (or conditions with overlapping symptoms) include a blood test for creatine kinase (CK) levels or MRI of the muscles.[10] If you are interested in being evaluated or finding out more about the diagnosis of TAM, we recommend asking your doctor for a referral to a specialist with experience in diagnosing myopathies and other muscle disorders.

Genetic testing for TAM may be possible, as currently there are 2 genes known to be responsible for TAM - the STIM1 and ORAI1 genes. However, some people with TAM do not have mutations in either of these genes. Additionally, specific mutations in these genes may alternatively be responsible for other disorders. The Genetic Testing Registry (GTR) provides information about the genetic tests available for TAM. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about genetic testing should contact a health care provider or a genetics professional.
Last updated: 12/27/2016
Currently, we are unaware of any targeted therapies for tubular aggregate myopathy. There is very limited information in the medical literature regarding the treatment or management of this condition. Supportive therapies may be recommended depending on the severity of symptoms and associated complications. High dose steroids were reported to be effective in one case of myopathy with tubular aggregates in 1991, but the reasons why were unclear.[11]
Last updated: 12/28/2016
The symptoms and severity of tubular aggregate myopathy (TAM) can vary from person to person, even within the same family.[2][4] Some individuals may even appear asymptomatic.[4] In general, the disorder is slowly progressive and chronic.[2] We are not aware of information in the literature regarding the life expectancy of people with TAM. However, we did not come across any reports of a shortened lifespan in affected individuals.
Last updated: 12/27/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
  • The U.S. National Institutes of Health, through the National Library of Medicine, developed ClinicalTrials.gov to provide patients, family members, and members of the public with current information on clinical research studies. There is a study titled Study of Inherited Neurological Disorders which may be of interest to you.
  • ClinicalTrials.gov lists trials that are related to Tubular aggregate myopathy. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Tubular aggregate myopathy. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Tubular aggregate myopathy:
    Congenital Muscle Disease International Registry
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Tubular aggregate myopathy. This website is maintained by the National Library of Medicine.
  • The Muscular Dystrophy Association has developed a resource called "Facts About Myopathies" that discusses commonly asked questions regarding myopathies. Click on the link above to view this information page.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
    Tubular aggregate myopathy 1
    Tubular aggregate myopathy 2
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Tubular aggregate myopathy. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My grandson's father has this disease and I am concerned about it being passed down to him. Can you please let me know what we can do to have him tested for it without a muscle biopsy? Also what exactly is the overall prognosis? See answer

  • I have tubular aggregate myopathy and am taking meloxicam. I am wondering if there is anything else I can take besides meloxicam. I have read about the side effects and this is why I am asking. I have recently started taking Karate and feel good when I take it. How much exercise is too much? See answer


  1. Tubular aggregate myopathy. Genetics Home Reference. October, 2014; https://ghr.nlm.nih.gov/condition/tubular-aggregate-myopathy#.
  2. Gilchrist JM, Ambler M, Agatiello P. Steroid-responsive tubular aggregate myopathy. Muscle & Nerve. 1991 Mar; 14(3):233-6. http://www.ncbi.nlm.nih.gov/pubmed/?term=2041544.
  3. Chevessier F et al. The origin of tubular aggregates in human myopathies. J Pathol. 2005 Nov; 207(3):313-23. http://www.ncbi.nlm.nih.gov/pubmed/16178054.
  4. Cassandra L. Kniffin. MYOPATHY, TUBULAR AGGREGATE, 1; TAM1. OMIM. April 7, 2015; https://www.omim.org/entry/160565.
  5. Cassandra L. Kniffin. MYOPATHY, TUBULAR AGGREGATE, 2; TAM2. OMIM. March 25, 2015; http://omim.org/entry/615883.
  6. ORAI1. NCBI Gene. December 18, 2016; https://www.ncbi.nlm.nih.gov/gene/84876.
  7. Böhm J et al. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet. 2013 Feb; 92(2):271-8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567276/. Accessed 8/15/2014.
  8. Pandit L, Narayanappa G, Bhat I, Thomas V. Autosomal recessive tubular aggregate myopathy in an Indian family. European Journal of Paediatric Neurology. 2009 Jul; 13(4):373-5. http://www.ncbi.nlm.nih.gov/pubmed/?term=18684652. Accessed 8/15/2014.
  9. Lee JM, Noguchi S. Calcium Dyshomeostasis in Tubular Aggregate Myopathy. Int J Mol Sci. November 22, 2016; 17(11):
  10. Valeria Beltrame et al. Muscle MR Imaging in Tubular Aggregate Myopathy. PLoS One. 2014; 9(4):e94427.
  11. Gilchrist JM, Ambler M, Agatiello P. Steroid-responsive tubular aggregate myopathy. Muscle Nerve. 1991 Mar;; 14(3):233-236. http://www.ncbi.nlm.nih.gov/pubmed/2041544.
  12. Johann Böhm et al. Clinical, histological and genetic characterisation of patients with tubular aggregate myopathy caused by mutations in STIM1. J Med Genet. 2014; 51:824-833.