practical information for female carriers of ald

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ALD LIFEPO BOX 43642LONDONSE22 OXR

Tel: 020 8473 [email protected]

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PRACTICAL INFORMATION FOR FEMALE CARRIERS OF ALDregistered charity number 1106008

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PRACTICAL INFORMATION FOR FEMALE CARRIERS OF ALD

You have discovered you are a carrier of a mutation in the ABCD1 gene, the gene which causes ALD (adrenoleukodystrophy).

This will most likely be because a family member has been diagnosed with either ALD (adrenoleucodystrophjy) or AMN (adrenomyeloneuropathy).

ALD Life is Britain’s leading charity dealing with these illnesses, run by people who have been in the situation you are now facing and who can help you.

We were founded to help and support people in your position. Our members have been through the same ordeal and have experienced the problems you now face.

Our members have helped compile this leafl et, which is packed with information patients in your position wish they had been told.

We must stress there is no right or wrong way of dealing with being a carrier but in researching this booklet, we have spoken to many who have been found to be carrying the ALD gene and have collated much of the information they wished they had been given to help them through fi rst stages.

We have a worldwide contact list of people who are willing to chat about all aspects of living with the disorder.

Introduction

I TRAWLED THE INTERNET MYSELF AND FOUND DANGEROUS INFORMATION. IT WOULD HAVE BEEN GOOD TO GET A RELIABLE AND TAILORED INFO CENTRE LIKE ALDLIFE,

Parent’s tip

Please contact ALD Life on 020 8473 7493 or email [email protected] website is www.aldlife.org

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Carrying a mutation in the ABCD1 gene puts you at risk of developing AMN, but it is not inevitable. Men are more likely to develop AMN than women and the symptoms of AMN usually develop at a younger age, and progress more quickly, in men than women.

Symptoms may include leg stiffness, progressive spastic paraparesis (stiffness, weakness and/or paralysis) of the lower extremities, and ataxia, a neurological condition that results in a lack of coordination of muscle movements.

Mobility in those with AMN can gradually deteriorate to the point where the sufferer develops increasing problems with mobility and may become wheelchair bound in very rare cases.

In AMN, there is damage to the axons of the nerve cells which control the muscles. Axons are the parts of the nerve cells which transmit information around the nervous system. The nerves that run down to your arms or your legs are made up of bundles of axons. The axons carry information as electrical impulses: myelin acts like an fl ex in an electric cable and is wrapped around the axons allowing them to carry information quickly and accurately.

In AMN these axons are damaged and can die back. The longest axons, the ones to

Will i develop amn symptoms? the legs, seem to be prone to damage in AMN and this is why in this disorder you usually begin to notice problems with your lower limbs. The nerves to the bladder, bowel and sexual organs are also affected.

In rare cases females who are ALD carriers can suffer with mental health problems.

ALD Life has produced separate leafl ets for men and women suffering the symptoms of AMN.

How can i prevent these symptoms?

There is currently no method of prevention or prediction for symptoms of AMN. Some choose to follow a very low fat diet and to take Lorenzo’s Oil to lower their very long chain fatty acid levels, which will normally be high, but there is no clinical evidence to suggest this is a successful treatment and it is purely a lifestyle choice.

Exercise is important for everybody, but some women do choose to make sure their exercise regime includes stretching exercises to ensure their muscles are in the best shape possible in case they suffer future symptoms.

Will i have adrenal failure?

Primary adrenal insuffi ciency - known also as Addisons disease – is caused when the adrenal glands do not produce enough of certain hormones. Symptoms include chronic fatigue, muscle weakness and

weight loss. People with adrenal failure can become extremely unwell very quickly if they get a viral or bacterial infection.

Males with the ALD gene can suffer from adrenal failure and should go to their doctor to be tested for this. It is extremely rare for females with the ALD gene to suffer from adrenal failure and routine testing is not required.

What medical follow up should i get?

Your GP will be able to refer you to an AMN specialist. They will ask you about AMN symptoms, examine you and check some blood tests. If you do go on to develop symptoms your specialist will recommend treatments to ease these. You can also discuss options for pregnancy.

If you are male you will also be given a special blood test, a short synacthen test, to check you for adrenal failure, which, if undetected and left untreated can be life threatening.

Should i have childern in the future?You have been diagnosed as a carrier of ALD and as a result you could pass the gene on to your children. You may already have children and they need to be assessed to see if they are carrying the ALD gene.

ALD and AMN are x linked genetic disorders. Upon diagnosis, you may want to consider genetic counselling. Although there are clinical and reproductive implications not everyone feels the same way about testing. However, ALD Life would recommend you should be offered genetic counselling and have your immediate family, siblings and especially any children tested immediately

Female carriers of the ALD gene can pass the gene on to sons or daughters and so need to consider their options carefully when having children. If you are a male with the gene you can only pass it on to your daughters but should also consider your options very carefully.

Although men cannot pass the gene on to male children, they can pass the gene on to female children who then have a 50/50 (1 in 2) chance of passing it on to their own children. If you are a female carrier and have a boy there is a 50-50 (1 in 2) chance that he could suffer from the life-threatening disease ALD as a child or from AMN in later life.

Similary if you have a girl there is a 50-50 (1 in 2) chance that you will pass the ALD gene to your daughter who in turn could suffer from the disorder and pass it on to her children.

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Explanation of the genetic implications

ALD is an X-linked disorder, which means that the genetic abnormality is on the X-chromosome. Women have two X-chromosomes, men only one. In women, the affected X-chromosome, the one with the gene for ALD (Figure 1, red chromosome), has less effect because of the presence of a normal copy of the gene (black chromosome) on the other X-chromosome. Men have one X-chromosome and one Y-chromosome (Figure 2). In men who have an X-chromosome for ALD, there is no other X-chromosome for protection; therefore symptoms are more severe in males.


Figure 1:

If a woman is a carrier for ALD she has the following possible outcomes for each child. When the child is a daughter, there is a 50% chance that she will be a carrier for ALD and a 50% chance that she will be unaffected. When the child is a boy, there is a 50% chance that the son will be affected (and at risk of developing either ALD or AMN) and a 50% chance that he will be unaffected.

Figure 2:

If an affected man has children, then all of his sons will be unaffected (he always passes his Y-chromosome to his son), but all of his daughters will be carriers (he always passes his only X-chromosome to his daughter).

carrier

carrier not a�ected X-ALD not a�ected

not a�ected

X-ALD X-chromosomenormal X-chromosomeY-chromosomeFemaleMale

not a�ected

carrier carrier not a�ected not a�ected

X-ALD

X-ALD X-chromosomenormal X-chromosomeY-chromosomeFemaleMale

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This treatment should be available on the NHS and your genetic counsellor should be able to direct you to a centre that can carry out this treatment. If you decide that PGD is something you are interested in pursuing, the PGD centre will make an application for funding to your local funding body.

The success of PGD is related to female age so most centres will only offer treatment to women under the age of 40 (or less).

ALD life knows of a number of families who have had children using the above techniques and are willing to talk about their experiences.

Some women who have been found to be carriers have advised that it helps to have counselling or someone to talk to. In some cases where one child is found to have the gene and another doesn’t have it, this may cause a strain in relationships.

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GIRLS ARE ALREADY SELF-CONSCIOUS AND BEING A CARRIER IS AN ADDED BURDEN. WHEN I BROKE UP WITH MY EX I THOUGHT NO ONE ELSE WOULD WANT TO BE WITH ME WHICH WAS A SILLY GIRLY THING AS I FOUND A GUY WHO LOVES ME AND ACCEPTS ALL THAT COMES WITH ME.

MY FAMILY TELL ME THEY THINK PART OF THE REASON MY SISTER STRUGGLES TO KEEP IN TOUCH WITH ME IS BECAUSE SHE FEELS BAD SHE ISN’T A CARRIER AND I AM. I FEEL THAT’S SAD IF IT IS THE CASE AS I HOLD NOTHING AGAINST HER.

Some people will choose to go ahead and have a child and take the risk of passing on the ALD gene.

Another option would be to have a test during pregnancy (prenatal diagnosis) to fi nd out whether or not your unborn baby has the ALD gene.

Two main tests are available: Chorionic villus sampling (CVS) which is done at around 12 weeks of pregnancy or Amniocentesis which is done at 16 weeks of pregnancy. Both tests carry a small risk of miscarriage at 2% (1 chance in 50) or 1% (1 chance in 100) respectively. The results would be available about one week after the test and you can then take the decision whether to carry on with the pregnancy.

There are also other tests now that can detect the sex of a pregnancy at an early stage e.g. nine weeks by testing a maternal blood sample. Some women will opt for this test fi rst and only go on to have a prenatal test if the test shows the pregnancy is male. We would recommend that you investigate Free Foetal DNA tests. The SAFE research group have a website that provides information on this subject -The Special Non-Invasive Advances in Fetal and Neonatal Evaluation NetworkWebsite: http://www.safenoe.org

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 in a “test tube”.

The embryos are then tested to detect whether they carry the mutated ABCD1 gene. In this way they can differentiate affected from unaffected male foetusess and carrier from non-carrier female foetusess. Only embryos that are proved not to be affected will be used to transfer to the woman’s womb with the hope that she will become pregnant.

Are there any options available so i can have children who are not affected by the ald gene?


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More information

ALD LifeALD Life was founded by Sara Hunt after both her sons were diagnosed with ALD. She has fi rst hand experience of most aspects of dealing with the disorder: her elder son, Alex, has symptomatic ALD and was diagnosed at age 7 in 2001 and is still with us today. Her younger son, Ayden, had a bone marrow transplant in 2008 and is no longer in danger of becoming symptomatic. The charity provides emotional and fi nancial support for all those affected by ALD and AMN.

www.aldlife.orgTel: 020 8473 7493

Email: [email protected]

Pre-Implantation Genetic Diagnosis:Guy’s and St Thomas’s Hospital in London run one of the world’s leading Pre-implanation Genetic Diagnosis units and have produced an online brochure with lots more detail on PGD.

www.guysandstthomas.nhs.uk/resources/services/managednetworks/womens/acu/pgd.pdf

The Human Feritlisation and Embryology Authority

can give you details of Pre-implantation Genetic Diagnosis services near to your area and give advaice on funding

www.hfea.gov.uk

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

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

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

Tel: 0141 211 0505Fax: 0141 211 1139

practical information for female carriers of ald

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