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Disease Profile

Tubular aggregate myopathy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Childhood

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ICD-10

G71.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Myopathy, tubular aggregate

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

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]

Symptoms

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]

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.

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

Cause

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.

Diagnosis

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.

Treatment

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]

Organizations

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.

Social Networking Websites

    Organizations Providing General Support

      Learn more

      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.

          References

          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. https://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. https://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; https://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. https://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. https://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. https://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.

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