Practical information for women with AMN (Adrenomyeloneuropathy)

AMN is caused by a genetic fault – scientists and doctors refer to this as a genetic mutation Affected people are unable to process natural molecules called very long chain fatty acids (VLCFAs). Instead of being broken down, VLCFAs accumulate in the body and damage the nerves. The gene at fault is called ABCD1. For simplicity we will refer to the faulty version as the ‘ALD/AMN gene’.

In AMN, there is damage to the nerve cells that control the muscles. These nerves run down your spinal cord to your arms and legs. The nerves are coated with a fatty substance called myelin, which allows nerve signals to be transmitted quickly and accurately. In AMN these long nerve cells (called axons) are damaged and can die back. Myelin is also lost. As a result, signals from the brain do not reach the muscles in the way they should, and your body’s functioning is affected.

The nerves supplying the legs are the most prone to damage.  AMN can also affect the nerves to the bladder, bowel and sexual organs.

The ALD gene affects men and women differently. The reasons for this are explained in the section on genetics.

In boys and men with the ALD gene, the nerves in the brain can be affected. This can lead to cerebral ALD (a severe degenerative disease that usually affects young boys). Males also often develop adrenal insufficiency (also called Addison’s disease). This is a potentially dangerous condition where the adrenal glands do not produce enough of some essential hormones. It is treated by taking replacement hormone tablets. In women, the development of either cerebral leukodystrophy or adrenal insufficiency is extremely rare –and has only been described in a very few isolated cases.

Previously, women with the ALD/AMN gene mutation were 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 faulty gene does cause effects in many women.

There are no exact figures, but 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 years, but can begin earlier or later.

Symptoms of AMN usually 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’. Most people also experience problems with their feet. Damage to the nerves supplying the legs affects the ability to balance, so unsteadiness and falls are common.

The nerves to the bladder, bowel and sexual organs can also be affected, which can result in urinary and bowel problems.

In some women the symptoms of AMN are very mild, and progress very slowly. Others are affected more severely. In rare cases, mobility can deteriorate to the point where the woman needs to use a wheelchair. It’s not possible to predict in advance how your AMN symptoms will progress.

After being diagnosed with AMN, you will be seen regularly by a specialist who will monitor your condition and any deterioration. They may arrange tests to look at the function of your nerves and spinal cord. Although you may have an MRI scan done as part of the initial tests to make the diagnosis, the brain is not affected in women with AMN and regular brain scans are not required.

Your specialist will advise you about treatment options for your symptoms.

If this is the first instance of AMN or ALD in your family, it is very important that you are offered genetic counselling to talk about testing for family members, especially if there are any young boys, or young women planning a pregnancy, in the family. Click here for information on genetic testing.

Your GP should be able to refer you to an AMN specialist. They will ask you about AMN symptoms, examine you and do some blood tests. If you do go on to develop symptoms, your specialist will recommend treatments to help with these. You can also discuss options for pregnancy. If your GP is unsure, we can help to find a local specialist for you.

Consult your doctor if you have any bothersome symptoms such as urinary and bowel problems – there are medications and treatments that can help. Medications can also help with muscle tightness and painful or restless legs. Ask to be referred to physiotherapy and occupational therapy if you have problems with balance or walking.

For reasons we don’t understand, the ALD gene affects people in different ways. Some males develop cerebral ALD as boys. Others have no symptoms in childhood, then develop AMN as adults. Some males develop adrenal failure (Addison’s disease) in addition to cerebral ALD or AMN.

About 80% of females with the gene will develop some AMN symptoms later in life. Symptoms can vary in severity. In women, the development of either cerebral leukodystrophy or adrenal insufficiency is extremely rare –and has only been described in a very few isolated cases.

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. You can be put in touch with others by contacting our support services.

There are lots of things you and your health team can do to help you live with AMN more easily. These are described later in the booklet.

In some women the symptoms of AMN are very mild, and progress very slowly. Others are affected more severely. In rare cases, mobility can deteriorate to the point where the woman needs to use a wheelchair. It’s not possible to predict in advance how your AMN symptoms will progress.

Lorenzo’s oil is a blend of four parts glycerol trioelate oil and one part glycerol trierucate oil. It was developed to try and correct the biochemical abnormalities in the blood that are associated with both AMN and ALD, i.e. raised levels of very long chain fatty acids (VLCFA).

Although treatment with Lorenzo’s oil, along with a special diet, does correct the blood abnormalities, it unfortunately has little effect on the disease. Clinical research has shown no evidence of benefit from Lorenzo’s oil in AMN, and it is therefore not recommended as a treatment.

You can see more about Lorenzo’s oil here.

Try and stay as healthy as you can in every way. Try not to get overweight, as this will put added strain on your legs and impede your mobility. Try and eat a good, nutritious diet that’s high in vegetables and fruit and low in sugary, fatty and highly processed foods. That doesn’t mean denying yourself treats but do try to eat sensibly.

We would advise anyone with AMN to develop an exercise and stretching programme. The more you can keep your body in good condition, the better you will be able to cope with the problems AMN will cause. As well as the physical benefits, exercise gives you a psychological boost too.

Even if you have never exercised before, it’s not too late to start. Always start slowly and consult your doctor before beginning any new exercise.

• Everyday things like taking a brisk walk most days, climbing stairs and cycling will help keep you in shape.
• Your local gym or leisure centre should be able to advise on exercise programmes for people with mobility problems to strengthen core muscles. Water-based exercise like Aquafit or swimming can be especially effective. Sometimes your GP can refer you to these sessions.

• Pilates is a physical fitness system that works on your core muscles. Walking awkwardly puts a lot of stress on your back. With a condition like AMN, the more you can strengthen these muscles, the better. Some people also find yoga is helpful.

It’s important to work on your flexibility. The biggest problem with AMN is often that your leg muscles become spastic, which means they are stimulated by your nervous system into behaving as if they are under tension all the time. Physiotherapists call this ‘excess tone’.

• Stiffness in the legs is usually worst when you get up in the morning. This is because your nervous system has been stimulating your leg muscles during the night.
• It helps to develop a stretching programme, with advice from your physiotherapist, and carry it out regularly. Yoga can also be helpful.
• Some people with AMN recommend a type of massage bed that combines cycloidal massage and infra-red treatment to help relieve the effects of spasticity

AMN affects your balance, and you may have problems with falling over.

Most people with AMN have problems with their feet. One particular problem is due to spasticity the persons toes may bend awkwardly into a claw-like position. This causes loss of balance and can make the person more unstable leading to trips and falls. In addition, because the nerves to your feet are damaged you may not be fully aware of pain or heat, putting you at risk of damaging your feet.

If you have foot problems, you should be referred to an orthotics department. The orthotist can make customised inserts for your shoes to assist you. Even small things like inserts can really help.

• Some people find simple aids such as a walking stick are sufficient to begin with, but you may need further help later on.
• It can be advisable to use a stick when you first begin to experience walking difficulties, as walking awkwardly can put undue pressure on your joints. The support given by a stick can reduce this.
• Some people with AMN use functional electrical stimulation (FES). A piece of equipment strapped to your leg gives out electrical pulses that help your foot to lift as you walk. It is now available from some NHS clinics. Ask your doctor about getting referred for assessment to see if this could be for you.
• A new walking aid called Musmate is more useful than FES for some people.

Incontinence is a problem for anyone with a neurological condition affecting the spinal cord and pelvic nerves. Unfortunately, people with AMN often suffer from bowel and urinary problems. Urinary urgency (the need to rush to the loo straight away) is common, and sometimes people do not make it in time. Constipation is very common.

It is one of those sensitive areas that people find it difficult to talk about, but treatments are available. It is important to discuss these issues with your doctor, who can refer you to a urologist or continence advisor if necessary. There are several treatments and medications which can help with urinary problems and make a huge difference to your quality of life.

For a small fee you can get a RADAR key, which lets you use accessible toilets for people with disabilities. There are over 9000 of these in the UK; they are kept locked to prevent vandalism and misuse. To find out more, visit the RADAR key page. Alex TLC can also provide you with a card explaining that you have a condition causing urgent need to use a toilet. Most shops and other premises will allow you to use their facilities upon production of the card.

There are a few important things to know about the ALD gene:

It affects males and females in different ways

It affects individuals in different ways

The chances of the gene being passed on to an affected person’s sons and daughters are known.

ALD is a X-linked disorder

The ALD gene sits on the X-chromosome. Women have two X-chromosomes, whereas men have an X and a Y. We inherit one of these chromosomes from each parent.

A female who inherits an X chromosome with the ALD gene also has a normal X-chromosome from her other parent. This partially compensates for the genetic fault, so females do not experience the most severe forms of ALD. (Because the gene is so rare, it is extremely unlikely that a female would inherit it from both parents.) Women can pass the gene to their children, hence why the term ‘carrier’ is sometimes used. However, we now know that the ALD gene does cause effects in many women, therefore, we refer to females as ‘females with the ALD gene’.

Males who have the gene don’t have a normal X-chromosome to compensate, so they are at risk of being severely affected.

How is ALD passed on?

The diagrams below show how the ALD gene is passed on. X-chromosomes with the ALD gene are shown in red.

From men

If a man with the gene has children, all of his sons will be free of the gene, because sons always get their father’s Y-chromosome, not the X.

All of his daughters will have the ALD gene, because fathers always pass their only X-chromosome to their daughters.

For reasons we don’t understand, the ALD gene affects people in different ways. Some males develop cerebral ALD as boys. Others have no symptoms in childhood, then develop AMN as adults. Some males develop adrenal failure (Addison’s disease) in addition to cerebral ALD or AMN.

About 80% of females with the gene will develop some AMN symptoms later in life. These are usually mild. In extremely rare cases women are diagnosed with adrenal insufficiency. Females do not suffer from cerebral ALD.

If you have been diagnosed with AMN, you have the ALD gene. There is a 50-50 chance of passing the gene on to any children you have. The section on genetic testing explains this in more detail.

Genetic testing

If this is the first instance of ALD/AMN in your family, you should be offered genetic counselling. Your GP or specialist can put you in touch with a genetic counsellor. The counsellor will ask about your family and identify anyone who is at risk of having the gene. We also have a booklet for females with the ALD gene.

• If you have young sons, we recommend that they should be tested for the gene as soon as possible. Boys with the gene are at risk of cerebral ALD, a devastating and fatal condition. It can be treated, but only if it is caught before obvious symptoms appear. Knowing about the gene means the boy(s) can have regular MRI scans, which will put them in the best possible position to have successful treatment if the need arises. Boys with the gene also need regular checks for adrenal insufficiency.
• It is also important to consider urgent testing if there are other young boys in the family, such as grandsons or nephews. Your brothers and sisters, and any adult children that you have, should all be offered genetic counselling. The genetic counsellor will talk them through the implications of testing so that they can make an informed choice about whether to be tested.
• Young females are not at immediate risk of developing symptoms and are not normally offered testing until they reach the age of 16, when they are able to understand the implications.

If you want to have children in the future, we strongly recommend that you talk to a genetic counsellor about your options. There are fertility treatments that can ensure that any children you have are free from the gene. However, these are not always funded by the NHS.

There is more information in our leaflet for Females with the ALD gene, on our Reproductive Options page, or you can look at the Guy’s and St Thomas’s hospital website at Pre-implantation genetic testing (PGT-M/SR) – Overview | Guy’s and St Thomas’ NHS Foundation Trust (guysandstthomas.nhs.uk). Alex TLC knows several families who have had children using fertility treatments and are willing to talk about their experiences.

Listed below are just some of the useful organisations that are there to help you:

ARC – Antenatal Results & Choices

A charity providing impartial information & individual support to parents whose unborn baby has been diagnosed with a condition that may lead to the decision to end the pregnancy.

www.arc-uk.org
Tel: 0845 077 2290

Pre-Implantation Genetic Diagnosis:

Guy’s and St Thomas’ hospital in London run one of the world’s leading pre-implantation genetic testing (PGT) units and have produced a website with lots more detail on PGT.

Pre-implantation genetic testing (PGT-M/SR) – Overview | Guy’s and St Thomas’ NHS Foundation Trust (guysandstthomas.nhs.uk)

The Human Fertilisation and Embryology Authority

The Human Fertilisation and Embryology Authority can give you details of pre-implantation genetic diagnosis services near to your area and give advice on funding.

www.hfea.gov.uk

What Clinic

What Clinic also have a list of centres around the UK offering PGD services.

www.whatclinic.com/fertility/uk/pgd- preimplantation-genetic-diagnosis

PGD in Scotland

PGD has been available in Scotland since 2002, based at Glasgow Royal Infirmary Assisted Conception Services Unit, Walton Building, 84 Castle Street, Glasgow, Scotland, United Kingdom, G4 0SF.

Tel: 0141 211 0505

https://www.nhsggc.scot/hospitals-services/services-a-to-z/assisted-conception-service/

You can get in touch with others in a similar situation and receive practical information, support and advice from us at Alex TLC. We also run an annual event which brings together families and individuals suffering from all aspects of living with the ALD gene to share experiences and learn about innovations in treatment and research.

Alex TLC was founded by Sara Hunt after both her sons were diagnosed with cerebral ALD. Our full time Support Services Manager provides practical, emotional and advocacy support to people and families affected by leukodystrophies including ALD and AMN. The charity also has a Grant scheme that can help with purchasing equipment that is not available through the statutory services, and can help with financial difficulties faced due to bone marrow transplant and bereavement.

Tel: 020 7701 4388

Email: info@alextlc.org

There are many charities that help people in your situation. Your social worker or occupational therapist should be able to give you a list of organisations you can apply to.

Please look on our useful links page for other organisations who may be able to help.

Carers Trust

Carers Trust is the largest provider of comprehensive carer support services in the UK.

It runs a network of 144 independently managed Carers’ Centres and provides quality information, advice and support services to over 400,000 carers.

www.carers.org

Tel: 0844 800 4361

Email: info@carers.org

Citizens Advice Bureau

Free information and advice on legal and money problems and can help you if you experience problems with benefits or housing. Your local branch can be found on the national website.

www.adviceguide.org.uk

Directgov

Government website for information about benefits and entitlements

www.direct.gov.uk

Disability Rights UK

Provides advice and support for disabled people on a wide range of issues from claiming the right benefits to employment and independent living.

Ground Floor, CAN Mezzanine, 49-51 East Rd London N1 6AH

www.disabilityrightsuk.org

Tel: 020 7250 8181

Email:

enquiries@disabilityrightsuk.org

Bladder, Bowel and other organs

Mobility

Asymptomatic ALD

Females with the ALD gene

If you need this practical information page printed out, we can print and send it to you, email us at info@alextlc.org