What is a carrier?
What are ALD and AMN?
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 and asymptomatic ALD.
What are the symptoms of AMN?
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.
Will I develop symptoms?
In the past, it was thought that women with the gene did not develop symptoms – hence the term ‘carriers’. 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.
Can I prevent symptoms developing?
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.
What medical follow-up should I get?
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.
How ALD/AMN is passed on: the genetics explained
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. Instead, they are said to be ‘carriers’. (Because the gene is so rare, it is extremely unlikely that a female would inherit it from both parents.)
Males who have the gene don’t have a normal X-chromosome to compensate, so they are at risk of being severely affected.
When a woman with the ALD gene has a daughter, there is a 50% chance the daughter will be a carrier 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.
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 be carriers, because fathers always pass their only X-chromosome to their daughters.
ALD is a X-linked disorder
The ALD/AMN 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. Instead, they are said to be ‘carriers. (Because the gene is so rare, it is extremely unlikely that a female would inherit it from both parents.)
- Males who have the gene don’t have a normal X-chromosome to compensate, so they are at risk of being severely affected.
How the gene is passed on
- When a woman with the gene has a daughter, there is a 50% chance the daughter will be a carrier and a 50% chance she will be unaffected (i.e. free of the gene).
- When a woman with the gene 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.
- 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 be carriers, because father always pass their only X-chromosome to their daughters.
The gene affects people in different ways
For reasons we don’t understand, the 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 will develop some AMN symptoms during their lifetime. These are usually mild.
What about my children
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.
- If you have young sons, we recommend that they should be tested immediately.
- If your young son is found to have the gene, it is important that he is referred to a specialist and started on regular monitoring, so that he can be treated if there are signs that cerebral ALD is developing. This is explained in another leaflet – Asymptomatic ALD.
- Adult sons should be offered testing after genetic counselling.
- Young females are not at immediate risk of developing symptoms. They are not normally offered testing until they reach 16, when they are able to understand the implications.
What about future pregnancy?
Both men and women with the gene may want to consider their options when thinking of having children. If you are a female carrier 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 be a carrier too, and in turn could pass the gene on to her children.
How can I make sure future children are free of the gene?
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. See this link for information for services provided by Guys and St Thomas’ https://www.guysandstthomas.nhs.uk/our-services/pgd/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.
Pre-implantation genetic diagnosis (PGD)
An alternative way of preventing an ALD pregnancy is pre-implantation genetic diagnosis (PGD). 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 PGD. This is because PGD can only be legally provided for certain diseases. Also, avoiding carrier status cannot be the primary purpose of PGD, but unaffected embryos can be preferred over carrier embryos when choosing embryos to transfer. The PGD centre or genetic counsellor will be able to explain the implications of this. PGD 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 PGD is related to female age, so most centres will only offer treatment to women under the age of 40 years.
Feelings about being a carrier
If you have an affected child
You may have been diagnosed as a carrier 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 are carriers 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.
Finding out that you are a carrier can be difficult news whatever your circumstances. Again, it can help to talk to others who are in the same situation. Alex TLC has lots of members who are living positively with the gene, including many who have gone on to have unaffected children.
Other organisations that can provide assistance
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.
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 diagnosis (PGD) units and have produced a website with lots more detail on PGD.
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.
What Clinic also have a list of centres around the UK offering PGD services.
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
Where can I get more information?
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 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
Where to find more help
These 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. Also, look out in your local library or online for a publication called Grants for Individuals In Need (www.grantsforindividuals.org.uk). This directory lists every relevant charity in the UK. Some charities require a referral from your social worker, but many will accept a letter from you setting out your case. We have listed some of the most useful organisations here.
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
Rights and benefits
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.
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
Equipment and financial support
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
Focus on Disability
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.
The motability charity helps provide wheelchair adapted cars, powered scooters and powered wheechairs for disabled people in the UK.
Tel: 0300 456 4566
- Brain (2014) X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Marc Engelen, Mathieu Barbier, Inge M. E. Dijkstra, Remmelt Schür, Rob M. A. de Bie, Camiel Verhamme, Marcel G. W. Dijkgraaf, Patrick A. Aubourg, Ronald J. A. Wanders, Bjorn M. van Geel, Marianne de Visser, Bwee T. Poll–The, Stephan Kemp
- Jangook P et al. Adrenoleukodystrophy in female heterozygotes: Underrecognized and undertreated. Molecular Genetics and Metabolism 105 (2012). 180–185.
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.
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