Adrenomyeloneuropathy

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AMN is caused by mutations in the ABCD1 gene. This gene is also affected in ALD, a serious degenerative disease that mainly affects young boys. In AMN, the damage happens in the nerves that control the muscles. It is impossible to predict how the gene will affect any one person, but males are more severely affected than females due to the fact that the condition has X-linked Inheritance.

This is a rare condition affecting less than 1 in 40,000 people.

Symptoms of Adrenomyeloneuropathy (AMN) can include stiffness, weakness and pain in the legs. This starts gradually and can progress over time. The medical term for this is ‘progressive spastic paraparesis’. Damage to the nerves supplying the legs means unsteadiness and falls are common. The nerves to the bladder, bowel and sexual organs can also be affected in AMN. Mobility can gradually deteriorate to the point where the sufferer eventually loses the ability to walk and becomes wheelchair bound. But this does not necessarily happen to all sufferers. AMN affects men more severely than women. Women with the gene are sometimes called ‘carriers’, because they can pass the gene to their children but were thought to be unaffected themselves. However, we now know that the gene does cause effects in many women. It is thought that about 80% of women with the gene will develop some symptoms of AMN during their lifetime. Symptoms usually start around the ages of 40 to 50, but can begin earlier or later.

As with ALD, in most males with AMN the adrenal glands are also affected. The adrenal glands make steroid hormones. Poor functioning of these glands is known as adrenal insufficiency, or Addison’s Disease. About 20% of men with AMN eventually develop some damage to nerves in the brain, which may result in dementia-like symptoms. Some men affected in this way go on to experience severe physical and mental deterioration, similar to that seen in boys with cerebral ALD.

Initial diagnosis is usually based on an MRI scan and a blood test for Very Long Chain Fatty acids (VLCFAs). High levels of VLCFAs, along with white matter deterioration in the brain, are good indicators of AMN being present. Diagnosis is confirmed by a genetic test. The genetic test takes some time – as much as six weeks to come back.

Once the genetic tests have confirmed the diagnosis, immediate family members should be offered urgent genetic testing

There are currently no drugs that can repair nerves or stop them from dying back, although research into treatments continues. However, drugs can help alleviate some of the symptoms of AMN, such as stiffness. These drugs seem to work for some people, but not for others. Discuss with your consultant the best treatments to help relieve your symptoms.

Progression of AMN to adult forms of cerebral ALD is potentially treatable with a stem cell transplant if it is detected early, although use of this treatment in adults is still experimental. If you would like to know more about this, talk to your consultant for the most up-to-date information. Transplants in adults who are showing signs of cerebral ALD are not common, but practices are changing. It is recommended that all cerebrally asymptomatic adults access yearly MRI scans if they want them.

Newborn Screening has been introduced in parts of the USA.

Once one member of a family has been diagnosed, it is very important to get the rest of your family checked genetically, especially if there are brothers, who could also have the disease.

When a boy is diagnosed with AMN it will most likely be inherited from his mother. You should be offered genetic counselling as soon as the diagnosis has been confirmed.

Genetic tests are advised for all siblings and parents. The genetic counsellor will talk you through the implications of the tests.

AMN is an X-linked disorder, which means that the genetic abnormality involves the X-chromosome.

Women have two X chromosomes. In women who carry the AMN gene mutation on one X-chromosome, the full-blown disease does not appear because there is a normal copy of the gene (Figure 1) on the other X-chromosome.

Men have one X-chromosome and one Y-chromosome (Figure 2). In men who have AMN on an X-chromosome there is no other X-chromosome for protection; therefore the male can develop symptomatic AMN.

For reasons we don’t understand, not all males who have the gene are affected in the same way. Some develop cerebral ALD as boys, others have no symptoms for many years and then develop AMN as adults. Some males develop Addison’s disease (adrenal failure) rather than ALD or AMN. Most women with the gene will also develop some, usually mild, AMN symptoms later in life.

Thank you to Alex TLC for helping provide this up-to-date information.

Established in 2004, Alex TLC provides support for all those with a genetic leukodystrophy and are also an internationally recognised centre of excellence for those affected with adrenoleukodystrophy and adrenomyeloneuropathy.

Alex TLC Contact Details:

• Phone 020 7701 4388
• Email info@alextlc.org
• Website https://www.alextlc.org/

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: APX010].