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Disease Profile

Inclusion body myopathy 2

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Adolescent

ICD-10

G71.8

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)

IBM2; Inclusion body myopathy, autosomal recessive; Inclusion body myopathy, quadriceps-sparing;

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders;

Summary

Inclusion body myopathy 2, also known as hereditary inclusion body myopathy (HIBM), GNE-related myopathy, distal myopathy with rimmed vacuoles, and Nonaka myopathy, is an inherited condition that primarily affects the skeletal muscles (the muscles that the body uses to move). This disorder is characterized by muscle weakness that appears in late adolescence or early adulthood and worsens over time.[1] Early symptoms typically develop in the 20s and 30s and may include difficulty running or walking, tripping, weakness in the index finger, and frequent loss of balance.[2] Inclusion body myopathy 2 is caused by mutations in the GNE gene. The condition is inherited in an autosomal recessive manner.[1] Treatment is focused on managing individual symptoms.[3]

Symptoms

Inclusion body myopathy 2 causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.The first sign of inclusion body myopathy 2 is often weakness of the tibialis anterior, a muscle in the lower leg that helps control up-and-down movement of the foot. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, inclusion body myopathy 2 usually does not affect the quadriceps (a group of large muscles at the front of the thigh). This condition also spares muscles of the eye or heart, and does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with inclusion body myopathy 2 require wheelchair assistance within 20 years after signs and symptoms appear.[1]

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
Fatty replacement of skeletal muscle
0012548
Foot dorsiflexor weakness
Foot drop
0009027
Mildly elevated creatine kinase
0008180
Muscle fiber inclusion bodies
0100299
Rimmed vacuoles
0003805
Tibialis muscle weakness
0008963
30%-79% of people have these symptoms
Absent Achilles reflex
Absent ankle reflexes
0003438
EMG: myopathic abnormalities
0003458
EMG: myotonic discharges
0100284
EMG: positive sharp waves
0030007
Hip flexor weakness
0012515
Hypothyroidism
Underactive thyroid
0000821
Increased variability in muscle fiber diameter
0003557
Limited shoulder movement
0006467
Limited wrist extension
0006251
Shoulder girdle muscle weakness
Weak shoulder muscles
0003547
Steppage gait
High stepping
0003376
5%-29% of people have these symptoms
Abnormal right hemidiaphragm morphology
0040047
Abnormality of the foot musculature
Abnormal foot muscles
0001436
Facial palsy
Bell's palsy
0010628
Lower limb amyotrophy
0007210
Scapular winging
Winged shoulder blade
0003691
Shoulder girdle muscle atrophy
Shoulder girdle muscle wasting
Shoulder-girdle muscle atrophy

[ more ]

0003724
1%-4% of people have these symptoms
Cardiomyopathy
Disease of the heart muscle
0001638
Distal lower limb muscle weakness
0009053
Weakness of long finger extensor muscles
0009077
Percent of people who have these symptoms is not available through HPO
Adult onset
Symptoms begin in adulthood
0003581
Autosomal recessive inheritance
0000007
Deposits immunoreactive to beta-amyloid protein
0003791
Distal amyotrophy
Distal muscle wasting
0003693
Distal muscle weakness
Weakness of outermost muscles
0002460
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
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288

Cause

Inclusion body myopathy 2 is caused by mutations in the GNE gene. The GNE gene provides instructions for making an enzyme responsible for making sialic acid, a simple sugar that attaches to the ends of more complex molecules on the surface of cells. People with inclusion body myopathy 2 have lower levels of sialic acid on the surface of certain proteins that are important for muscle function. This shortage of sialic acid leads to the progressive muscle wasting and disability seen in patients with inclusion body myopathy 2.[1][2] Researchers are currently working towards a better understanding of how this shortage of sialic acid leads to the progressive muscle weakness in people with this condition.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Currently, there is no cure and no way to prevent the progression of a Inclusion body myopathy 2.[2] Treatment is focused on managing individual symptoms. People with this condition are often evaluated and managed by a multidisciplinary team including neurologists and physiatrists, as well as physical and occupational therapists.[3]

    Researchers at Hadassah, USC, UCLA, UCSD, Johns Hopkins University, Canada, NIH, and Japan are contributing towards finding an effective treatment. Information about treatments which are on the horizon are described in a publication from the Advancement of Research for Myopathies which can be accessed by clicking here. 

    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.

    Organizations Supporting this Disease

      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 Inclusion body myopathy 2. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • 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. 
            The Online Mendelian Inheritance in Man (OMIM)
            The Online Mendelian Inheritance in Man (OMIM)
          • 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 Inclusion body myopathy 2. Click on the link to view a sample search on this topic.

            References

            1. Inclusion body myopathy 2. Genetics Home Reference (GHR). December 2008; https://ghr.nlm.nih.gov/condition/inclusion-body-myopathy-2. Accessed 12/4/2012.
            2. About HIBM. Neuromuscular Disease Foundation. https://www.ndf-hibm.org/index.php/about-hibm. Accessed 12/4/2012.
            3. O'Ferrall E, Sinnreich M. GNE-Related Myopathy. GeneReviews. August 2009; https://www.ncbi.nlm.nih.gov/books/NBK1262/. Accessed 12/4/2012.

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