What is GNE myopathy?

Signs and symptoms
Disease progression
Talking to your family
Getting Diagnosed
Diagnostic tools


Mutations in the GNE gene lead to GNE myopathy 1

GNE myopathy, also called Hereditary Inclusion Body Myopathy, or HIBM, is a rare, progressive muscle disease that affects both the upper and lower limbs.  A deficiency in sialic acid plays a role in the causation of the muscle disease. Sialic acid is an important substance made in the body that helps muscle proteins function properly. When sialic acid levels are low, the muscles begin to weaken, resulting in loss of strength and muscle function.1-3

It is thought that less than 2,000 people have GNE myopathy worldwide4

The muscle disease can affect anyone, although it appears to be more prevalent in people of Japanese, Middle Eastern, and Indian descent.2-4

GNE myopathy is inherited in an autosomal recessive manner3,5

Autosomal recessive describes the way the genes are passed down. Everyone carries a handful of recessive genes. If a person has only one copy of a recessive gene, they generally do not develop the disease associated with the recessive gene. However, if a person has two copies of an abnormal recessive gene, an autosomal recessive disease can develop. These recessive genes are inherited, or derived genetically from one’s parents.5,6

For a person to inherit GNE myopathy, they must get a copy of the abnormal GNE gene from each of their parents.6

Other names for GNE myopathy

While most commonly called GNE myopathy or Hereditary Inclusion Body Myopathy (HIBM), the muscle disease may also be referred to as1,2:

  • Distal Myopathy with Rimmed Vacuoles (DMRV)
  • Quadriceps Sparing Myopathy (QSM)
  • Hereditary Inclusion Body Myopathy Type 2 (HIBM2)
  • Inclusion Body Myopathy Type 2 (IBM2)
  • Nonaka Myopathy

If both parents are carriers of a GNE gene with mutations, there is a 1 in 4 chance a person will develop GNE myopathy.5

In a small portion of people, GNE myopathy occurs spontaneously—the mutation cannot be traced to either parent.7

Signs and symptoms of GNE myopathy

Though GNE myopathy is a skeletal muscle disease that affects all limbs, early signs and symptoms are generally walking-related3,8

GNE myopathy is a disease of progressive muscle weakness and atrophy that affects both the arms and the legs. People with GNE myopathy usually begin to exhibit symptoms, starting in the legs, in their twenties and thirties.1,8

Early symptoms typically include:

  • Foot drop (difficulty lifting the front part of the foot), which can cause tripping or lack of balance1
  • Other walking-related issues, such as difficulty climbing stairs or running8

Most initial symptoms begin with muscle weakness in the lower half of the body, though upper body weakness will occur as well.1

GNE myopathy generally starts in the lower legs, but spreads to involve the upper legs, hips, arms, shoulders, and hands.1

One unique feature of GNE myopathy is that the quadriceps muscles are relatively spared compared to surrounding leg muscles, which is why it’s sometimes referred to as “Quadriceps-Sparing Myopathy.”2,5,9

The quadriceps are a group of muscles on the front of the thigh. While most muscles in the lower body will significantly weaken and atrophy, the quadriceps are affected to a lesser degree.5,9
Specific diagnostic tools can show which muscles are being affected and which are being relatively spared (eg quadriceps) in GNE myopathy.
Learn more about diagnostic toolsLearn more about diagnostic tools

GNE myopathy disease progression

GNE myopathy is steadily progressive in the muscles of the arms and legs5,10

As GNE myopathy progresses, both the muscles in the upper and lower body will become severely affected. The disease follows a distinct path of progression1,9:

  • Lower body muscles are generally affected before upper body muscles
  • Limb muscles, like the hands and feet, are generally affected before muscles closer to the torso

As the disease progresses, various assistance devices may be used to aid movement, such as5,7:

  • Ankle braces to correct foot drop (called ankle-foot orthosis, or AFO)
  • Canes
  • Walkers

Due to the relative sparing of the quadriceps muscles, some people with GNE myopathy are able to maintain unassisted walking for many years. Cognitive abilities, coordination, heart function, swallowing, speech, and breathing generally remain unaffected.3,9,10

Talking to your family about GNE myopathy

Sharing your disease diagnosis can help the future of your loved ones

There is no shame in having GNE myopathy. Sharing your own diagnosis and educating your family members about the inherited nature of GNE myopathy may help them to take steps to find out their own risk for the hereditary disease. In turn, this can inform their lifestyle and health care decisions in the future. Learn about how to test for GNE myopathy.

A community of support

In addition to receiving support from your own family, there is a whole community of patient advocacy groups that support people with GNE myopathy and their loved ones. Learn about patient advocacy.

Getting diagnosed with GNE myopathy

Importance of an accurate diagnosis

In people with symptoms of GNE myopathy, a genetic test can help lead to accurate diagnosis.11

According to the AAN,* identifying progressive muscular dystrophies like GNE myopathy through genetic testing can help12:

  • Advise the future course of the muscle disease
  • Provide the optimal and most direct care
*AAN, American Academy of Neurology; the world’s largest association of neurologists and neuroscience professionals.

Challenges and delays to diagnosis

Most health care providers have little experience with GNE myopathy because it is so rare. On top of that, many types of muscular dystrophies have similar symptoms, so telling them apart can be challenging.11

Some diseases that share signs and symptoms with GNE myopathy include2:

  • Limb-girdle muscular dystrophy (LGMD)
  • Charcot-Marie-Tooth (CMT) disease
  • Other distal myopathies

Initially confusing GNE myopathy for another disease—coupled with the fact that a diagnosis may require the efforts of a multidisciplinary team such as primary care physicians, neurologists, and neuromuscular specialists—illustrates why a delayed diagnosis for GNE myopathy is common.

Ask your doctor if he or she thinks GNE myopathy genetic testing is appropriate for you.

GNE myopathy diagnostic tools

AAN guidelines for a complete diagnosis

For a complete diagnosis of any progressive myopathy, the AAN recommends obtaining the following information7:

  • Personal and family health history
  • Complete physical exam
  • Detailed knowledge of symptoms, including muscle weakness locations

To help accurately identify where muscle weakness is occurring, your doctor may use the following diagnostic tools:

MRIs and CT scans

Magnetic-resonance imaging (MRI) and computed tomography (CT) scans are diagnostic imaging procedures that allow doctors to examine muscles in great detail.13,14

These images reveal which specific muscles are being affected by GNE myopathy and which are being relatively spared (quadriceps).9

Huizing et al 2009.

Muscle biopsy

A muscle biopsy examines a small amount of tissue removed by a needle from an affected muscle.16

A biopsy of an affected muscle can show the presence of small, encircled cavities in the muscle fibers called rimmed vacuoles, a signature feature of cells in people with GNE myopathy.1

Note: It is very important that the biopsy is conducted from an affected muscle. A less affected muscle, such as the quadriceps, may not exhibit key signs of the disease.

Genetic testing

Genetic testing takes place when health care professionals look at DNA, via a simple blood test, to find changes in genes that can cause disease.

AAN guidelines recommend that your doctor order genetic testing to help confirm mutations in the GNE gene.7

Your doctor may also order an electromyogram (EMG), which tests neuromuscular activity, and/or a blood test to measure the amount of creatine phosphokinase (CPK) enzyme in the body to help with diagnosis.3,15

Use this discussion guide to have a conversation with your doctor about whether GNE myopathy genetic testing is appropriate for you.
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References: 1. Celeste FV, Vilboux T, Ciccone C, et al. Mutation update for GNE gene variants associated with GNE myopathy. Hum Mutat. 2014;35(8):915-926. 2. Nishino I, Carrillo-Carrasco N, Argov Z. GNE myopathy: current update and future therapy. J Neurol Neurosurg Psychiatry. July 14, 2014:1-8. doi:10.1136/jnnp-2013-307051. 3. Jay, CM, Levonyak, N, Nemunaitis, G, et al. Hereditary Inclusion Body Myopathy (HIBM2). Gene Regul Syst Bio. 2009;3:181-190. 4. Data on file. Ultragenyx Pharmaceutical Inc. 5. O’Ferrall, EK, Sinnreich, M. GNE-related myopathy. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle, 2013. 6. New South Wales Government. Centre for Genetics Education. Autosomal recessive inheritance—traditional patterns of inheritance 1. Fact Sheet 8. www.genetics.edu.au. Updated June 27, 2012. Accessed May 12, 2015. 7. American Academy of Neurology. Summary of evidence-based guideline for patients and their families: limb-girdle and distal muscular dystrophies. 2014. 8. Nonaka I, Noguchi S, Nishino I. Distal myopathy with rimmed vacuoles and hereditary inclusion body myopathy. Current Neurology and Neuroscience Reports. 2005;5:61-65. 9. Broccolini A, Mirabella, M. Hereditary inclusion-body myopathies. Biochim Biophys Acta. 2014:1-7. http://dx.doi.org/10.1016/j.bbadis.2014.08.007. 10. Huizing M, Krasnewich DM. Hereditary inclusion body myopathy: a decade of progress. Biochim Biophys Acta. 2009;1792:881-887. doi:10.1016/j.bbadis.2009.07.001. 11. American Academy of Neurology. Summary of evidence-based guideline for clinicians: evidence-based guideline: diagnosis and treatment of limb-girdle and distal muscular dystrophies. 2014. 12. Narayanaswami P, Weiss M, Selcen D, et al. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology. 2014;83:1453-1463. 13. Johns Hopkins Medicine. Computed tomography (CT or CAT) scan of the bones. www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=92,P07649. Accessed April 28, 2015. 14. Johns Hopkins Medicine. Magnetic Resonance Imaging (MRI). http://www.hopkinsmedicine.org/johns_hopkins_bayview/medical_services/lab_and_imaging_services/magnetic_resonance_imaging.html. Accessed May 26, 2015. 15. Johns Hopkins Medicine. What is EMG? www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=92,P07656. Accessed April 28, 2015. 16. Johns Hopkins Medicine. Muscle biopsy. www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=92,P07671. Accessed April 25, 2014.