The nerves to the bowel and bladder can also be affected. This can lead to constipation and problems with bladder control. See separate page for women who have symptoms of AMN.
This page is for you if you have discovered that you are a female with a faulty gene that causes the rare genetic conditions known as Adrenoleukodystrophy (ALD) and Adrenomyeloneuropathy (AMN)
You may have discovered this because a family member has been diagnosed with one of these conditions.
The gene affects males and females differently. Females 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 ALD gene does cause effects in many women, therefore, we refer to females as ‘females with the ALD gene’. It is thought that about 80% of women with the ALD 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.
This page explains the different forms of ALD and AMN and how females can be affected. We have produced a separate booklet for women with AMN.
In researching this booklet, we have spoken to many women who have discovered they have the gene, and have put together the information they wished they had been given. Of course, there is no right or wrong way of dealing with having the ALD gene, but we hope the information will be useful for you. The medical information has been compiled from reputable sources and checked by medical experts in ALD.
Alex TLC is Britain’s leading charity for leukodystrophies including ALD and AMN. It is run by people who have been personally affected by the conditions, either themselves or in their families, and are here to help you. Alex TLC provides practical, emotional and financial support for all those affected by ALD and AMN. We also have a worldwide contact list of people who are willing to chat about all aspects of living with AMN and can find out more here.
To get in touch please contact Alex, The Leukodystrophy Charity (Alex TLC) on 020 7701 4388 or email info@alextlc.org. Or visit our website at www.alextlc.org.
The gene responsible for ALD and AMN is called ABCD1, and it is located on the X-chromosome.
Females have two X-chromosomes, whereas males have an X and a Y. In females who have the faulty gene on one X-chromosome, the full-blown disease does not appear because there is a normal copy of the gene on the other X-chromosome to compensate. But 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’. There is more information about the genetic aspects of ALD and AMN further on in this page.
ALD and AMN are caused by a genetic fault (which doctors and scientists refer to as a genetic ‘mutation’) that stops the body from processing molecules called Very Long Chain Fatty Acids (VLCFAs). Instead of being broken down, VLCFAs accumulate in the body and gradually destroy the sheath that covers the nerves. This is made of a substance called myelin and acts like the coating around an electric cable, allowing messages to be transmitted along nerve cells. When the myelin is damaged, messages cannot get through and the person’s functioning is affected.
The gene at fault is called ABCD1. We will call the faulty version the ALD / AMN gene for simplicity. The gene can cause several related but different conditions. The most devastating form, symptomatic cerebral ALD, affects the brain and only occurs in males. If it is going to happen, it usually develops in childhood. Males with the gene often develop adrenal insufficiency (also known as Addison’s disease), which is dangerous if not treated. Males should have regular checks to monitor their adrenal function. Adrenal insufficiency caused by the gene is extremely rare in females, and monitoring is not necessary.
It can affect both men and women, though women are normally less severely affected, it is not possible to predict how the gene will affect any one person. See separate pages on symptomatic cerebral ALD and asymptomatic ALD.
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.
Symptoms of AMN can include stiffness, weakness and pain in the legs. This starts gradually and can progress over time. Damage to the nerves supplying the legs means people commonly experience unsteadiness and are prone to falling. Mobility can gradually deteriorate to the point where the person develops significant problems. In rare cases, women with AMN may eventually need to use a wheelchair.
The nerves to the bowel and bladder can also be affected. This can lead to constipation and problems with bladder control. See separate page for women who have symptoms of AMN.
There are no exact figures, but it is now thought that about 80% of females with the gene will develop some symptoms of AMN during their lifetime. The symptoms usually develop at an older age in women than in men, and progress more slowly. They typically start in the 40s or 50s, though they can begin earlier or later. Symptoms in girls in childhood are extremely rare.
For most affected women, symptoms are relatively mild. Women with the gene virtually never develop cerebral ALD or adrenal insufficiency – this has only ever been described in a very few isolated cases where the affected women were not tested for other causes- which means it is impossible to know whether or not they may have a second (co-incidental) cause for their symptoms.
There is currently no way to predict if or when women with the gene will develop symptoms.
Staying as healthy as possible and keeping active are the best things you can do. Some women choose do exercises to ensure their muscles are in good shape, so that they will be better able to deal with symptoms if they arise.
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.
There are a few important things to know about the ALD gene:
The ALD gene sits on the X-chromosome (ALD is sometimes called X-ALD). 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.
Males who have the ALD gene don’t have a normal X-chromosome to compensate, so they are at risk of being severely affected.
The diagrams below show how the ALD gene is passed on. X-chromosomes with the ALD gene are shown in red.
From women
When a woman with the ALD gene has a daughter, there is a 50% chance the daughter will have the ALD gene and a 50% chance she will be unaffected (i.e. free of the gene).
When the woman has a son, there is a 50% chance that he will have the gene and be at risk of severe effects. Because fathers don’t pass their X-chromosome to their sons, males have usually inherited the gene from their mother.
In rare cases, instead of being inherited, the gene mutation happens while the embryo is developing. This is called a ‘de novo’ mutation.
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. Symptoms can vary in severity. In females, the development of either cerebral leukodystrophy or adrenal insufficiency is extremely rare –and has only been described in a very few isolated cases.
If you have children, each child has a 50% chance of having the ALD gene. You may be reading this because the gene has been found in one of your children already. If you have children, we recommend that they should be tested for the gene.
Upon diagnosis you should be offered genetic counselling. The genetic counsellor will ask about your family and identify anyone who is at risk of having the gene. They can also arrange testing.
The idea of genetic testing for your children can be frightening. Of course, if they are adults, they will have to make their own decisions. The genetic counsellor will talk them through the implications of testing so that they can make an informed choice. Your GP or specialist can put you in touch with a genetic counsellor if you haven’t already been referred.
Both men and women with the gene may want to consider their options when thinking of having children. If you are a female with the ALD gene and have a boy, there is a 50% chance that he will be at risk of developing the life-threatening disease ALD as a child or developing AMN in later life. If you have a girl, there is a 50% chance that she will have the ALD gene too, and in turn could pass the gene on to her children.
Some people choose to go ahead and have a child, and take the risk of passing on the ALD gene. Another option is to have a test during pregnancy (prenatal diagnosis) to find out whether your unborn baby has the gene. A third option is to have pre-implantation genetic diagnosis, a form of IVF where embryos are tested before being implanted.
We strongly recommend that you talk to a genetic counsellor about your options if you want to have children. Alex TLC know several families who have had children using the techniques described here and are willing to talk about their experiences. There is more information on our Reproductive Options page, or you can find more information about services provided by Guys and St Thomas’ here https://www.guysandstthomas.nhs.uk/our-services/pgt/overview.aspx
Two main prenatal tests are available – chorionic villus sampling and amniocentesis Both require a sample of the baby’s DNA to be tested. Both procedures carry a small risk of miscarriage of 1%.
You can find out the sex of a pregnancy by a blood test on the mother, from about 9 weeks. Some women opt for this test first, and only go on to have a prenatal test if the pregnancy is male. Chorionic villus sampling (CVS) is done at around 12 weeks of pregnancy. Amniocentesis is done at 16 weeks. You don’t need both tests.
The results are available after about a week, and you can then take the decision on whether to carry on with the pregnancy.
If the pregnancy was male and had the ALD gene, you would be offered the choice of termination or continuing with the pregnancy, if you continue with the pregnancy then you would be advised to contact a specialist for guidance on a programme of surveillance. See information about Asymptomatic Males. This is a very personal decision to make. Alex TLC can put you in touch with others who have been in this difficult position.
An alternative way of preventing an ALD pregnancy is pre-implantation genetic testing (PGT). At-risk couples can use IVF technology (even though they do not have fertility problems) to create embryos. The embryos are tested, and only those that will not lead to an affected child are transferred to the woman’s womb.
Couples have to be assessed at a licensed centre before they can be offered PGT. This is because PGT can only be legally provided for certain diseases. Also, avoiding carrier status cannot be the primary purpose of PGT, but unaffected embryos can be preferred over carrier embryos when choosing embryos to transfer. The PGT centre or genetic counsellor will be able to explain the implications of this. PGT should be available on the NHS, and your genetic counsellor should be able to direct you to a centre that can provide it.
The success of PGT is related to female age, so most centres will only offer treatment to women under the age of 40 years.
You may have been diagnosed as a female with the ALD gene because you have a son who has the gene. Perhaps you have a son who has developed symptomatic cerebral ALD, or perhaps you are coming to terms with the fact that your son is at risk. These are devastating situations. One mother of a son with symptomatic cerebral ALD told us: “I grieved. I grieved massively for the future I had lost. I went through denial, anger, misery. Some women are broken by the news but eventually you do rally – somehow. I’m in a better place now.”
The uncertainty that comes from having a son at risk can also have a huge impact on the family.
Mothers who find out that they have the ALD gene may experience feelings of guilt that they have passed the gene to their children. It is very common to feel this way.
It is very important to take care of your own physical and mental wellbeing – both for your own sake and so that you can be the parent and carer that you need to be for your children. Don’t suffer in silence. It can help to talk to someone who has been through the same situation, and /or to a counsellor with experience in medical issues. Alex TLC can put you in touch with people or organisations who can help.
Listed below are just some of the useful organisations that are there to help you:
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
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.
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.
What Clinic also have a list of centres around the UK offering PGD services.
www.whatclinic.com/fertility/uk/pgd- preimplantation-genetic-diagnosis
PGT 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.
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.
Directgov
Government website for information about benefits and entitlements
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
Tel: 020 7250 8181
Email:
Disabled Living Centre (DLC)
A Disabled Living Centre (DLC) is where you can get free and impartial information and advice about products and equipment for disabled or older people. At a DLC you can see and try out products and explore other solutions. Centres provide free information to people in person, by telephone, letter or email.
Disabled Living Foundation
National charity that can help you find products and suppliers of equipment for disabled people. Also has an equipment demonstration centre.
Helpline: 0300 999 0004
Email: helpline@dlf.org.uk
Turn2us Grant Search
Turn2us grant search is an online tool which allows you to search for grants you may be eligible for. Visit Turn2us Grants Search to use the search engine.
https://grants-search.turn2us.org.uk/
Family Fund
Family Fund is a charity that provides grants and support services for families raising a disabled or seriously ill child or young person on a low income across the UK.
Motability Scheme
The motability charity helps provide wheelchair adapted cars, powered scooters and powered wheechairs for disabled people in the UK.
Tel: 0300 456 4566
If you need this practical information page printed out, we can print and send it to you, email us at info@alextlc.org
All the medical information on this site has been checked for accuracy by Alex The Leukodystrophy Charity (Alex TLC) board of medical experts but does not replace advice given from medical professionals involved with your care. Medical opinion should always be sought. The information is for general use only and is not intended to provide personal medical advice or substitute for the advice of your physician. Medical information changes rapidly and whilst Alex The Leukodystrophy Charity (Alex TLC) make every effort to update the content of the site, some information may be out of date. Remember to always seek the opinion of a medical doctor.
There are a number of links from this website to sites maintained by third parties. These links are provided purely to assist you, and in good faith. The presence of a link does not necessarily imply that Alex TLC endorses or supports those third parties.
Alex TLC cannot be held responsible for any damage or loss caused by any inaccuracy in this site, or in linked sites/pages