Genetic Screening and Counselling


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Incidence of Gauchers disease


This paper is prepared by Committee members of the Gauchers Association to provide guidelines to those with Gauchers disease, their families and medical advisers on the many issues involved in the genetic testing, screening and counselling of Gauchers disease. They have come to the following conclusions:

  1. General population screening, even in the Ashkenazi Jewish community, is not considered desirable or appropriate.
  2. Any programme or research project must have ethical approval.
  3. Research to help people with Gauchers disease and their families should come from information obtained from those who already have symptoms.
  4. No screening within families should be undertaken without full and proper consideration of the effects of any potential result. Counselling must be available prior to any screening.
  5. Screening must be voluntary, either as part of a diagnosis or initiated by the individual concerned. Pressure for screening of non-symptomatic individuals should not come from external sources eg other relatives, researchers, doctors.
  6. Concerned individuals should be given the opportunity to meet those with Gauchers disease and their families as part of the counselling process.

Genetic screening or testing is a process to analyse blood or skin samples in order to identify people who have Gauchers disease, who are healthy carriers of the disease or who do not have, or carry, the disease. The term testing is usually used when seeking to identify individuals or those within a family, screening when analysing samples from a larger group of people, perhaps within a population. However both these terms are often used to describe the same thing as the process and intent is the same: to discover if someone has Gauchers disease or is a healthy carrier.

Currently screening is carried out by enzyme studies (non-genetic) and in some cases by DNA studies (genetic).

Enzyme studies show the level of glucocerebrosidase (the enzyme which is deficient in those with Gauchers disease) in blood and skin samples. Those people with a low level (less than approximately 20%) have the disease, those with an intermediate level (20-70%) are carriers and those above these levels do not have the disease. There is however an overlap in these studies between those affected and carriers, and between carriers and those unaffected, possibly up to 20%. Therefore although an enzyme study is reliable for the diagnosis of someone suffering from the symptoms of Gauchers disease, it is unreliable for the detection of carrier status.

DNA studies examine the different mutations of the gene for glucocerebrosidase, which can cause Gauchers disease. Every person inherits two genes, one from each parent (known as their genotype). If both genes are mutated, the person may have the disease or may have the genetic markers for the disease but may not experience any symptoms now or in the future. If only one gene is mutated, the person is a healthy carrier. The genes are located on DNA material which can be analysed from blood samples.

Over 150 different mutations have already been discovered but only four of these account for 97% of the mutations in Ashkenazi Jewish sufferers and about 60% in patients in the general population (Beutler).

DNA studies in the UK are carried out routinely on nine mutations at the Willink Institute, Manchester five mutations at Addenbrooke's Hospital, Cambridge and on four mutations at Great Ormond Street Hospital, London. All centres can screen for more mutations. Other centres can send samples to these three centres for testing.

Thus, in the UK, sufferers can be tested for the most common mutations to see whether they have any of these mutations (they may have two of the same or two different); and carriers can be tested to see if they have one of these mutations. However if sufferers or carriers have one of the less common mutations or one that is not yet discovered, these will not be identified.

One of the most common mutations is N370S or 1226G. If someone has inherited two copies of this mutation, this often leads to a mild form of the disease; indeed up to 75% of people who inherit them may never show any symptoms; but this combination may also cause severe disease.

However if N370S pairs with another mutation eg L444P, or there are combinations of other mutations, the severity can be more accurately predicted although yet again symptoms can vary significantly. It should be noted that if one of the mutations is N370S, the disease will remain as Type 1 with no neurological symptoms and will not develop into Types 2 or 3. See bottom of page 2 for more details about the different types of Gauchers disease.

Because of the variability of symptoms suffered by those with Gauchers disease with the same genotype, caution should be shown when predicting the progress of the disease based on mutational analysis. There are probably additional factors, either genetic or environmental, why two people, even siblings, have inherited the same mutations but may have widely different severity of symptoms.

A comparison of enzyme and DNA studies
Based on a summary by Dr Ian Ellis

  Enzyme studies DNA studies
Diagnosis yes yes
Severity & prognosis no help helpful#
Family carrier detection 20% overlap available*
Pre-natal diagnosis yes available*
Population screening no debatable

#May be helpful. *For some but not all mutations.

Genetic counselling provides information, discussion and support to patients with Gauchers disease, their families and other interested parties.

Counselling is very important and must be provided prior to and alongside any screening. Positive test results can cause distress and in some cases, screening may be unnecessary. Adequate time for counselling must be given to avoid the sufferer or family coming away confused by the consultation. Counselling may need to continue afterwards.

The Gauchers Association enables sufferers and their families to talk to others who have gone through the same experiences and receive more information and support.

Counselling should include:

Insurance, Pensions and Job Applications There are currently disadvantages for someone to be tested for Gauchers disease and found to be genetically positive to the test but show no symptoms as he/she may be obliged to disclose this information on a proposal form for life insurance (possibly when applying for a mortgage).

Given the rarity and variability of the disease and the cautiousness of life insurance companies, this could lead to a premium loading or even refusal of cover. Once this has occurred, the refusal or loading would have to be disclosed on any future application which would make it even more difficult to obtain cover.

Similar considerations could apply with a pension scheme or with a company which requires employees to have a medical. This could result in someone being excluded from the pension scheme or even refused employment.

Other types of insurance policies like medical insurance (eg BUPA) and permanent health (for the self employed) are also likely to be refused on the grounds that symptoms may appear later or alternatively the condition may be excluded from the insurance cover.

The Purpose of Genetic Screening in Different Groups of Individuals

1. To confirm the diagnosis in patients with symptoms.

Genetic testing may be useful for patients with symptoms who are suspected of having Gauchers disease. Determining their genotype through DNA analysis may also help doctors decide how the disease may progress and what treatment should be offered. Counselling must be available for the patient and immediate family.

Further, every GP and hospital doctor should be made aware that if certain signs or symptoms occur eg enlarged spleen or liver, blood disorders, bone pain, bone deterioration, Gauchers disease should be considered. Symptoms can be described as what the patient complains about eg pain, heavy bleeding, tiredness; signs are what the doctor finds eg in blood tests and X-rays, feeling the patient's stomach.

2. In families of a diagnosed patient, to advise other family members whether they also have the disease (or have genetic markers for the disease even if they don't have symptoms), are carriers or are neither.

Parents Both parents of a sufferer must be carriers or they might have the disease (or carry genetic markers for the disease even if they don't show symptoms). DNA testing will possibly discover each parent's status (genotype). Parents may wish to have counselling with a view to having more children (especially in Types 2 and 3 and the more severe cases of Type 1). This is discussed more fully in Note 3 below.

Siblings (brothers and sisters) may be tested to discover if they also have the disease, have the genetic markers for the disease, are carriers or are neither. If symptoms appear, they should be tested. Also if siblings or their relatives are concerned about their future, counselling should be sought together with possible testing. However prior to testing, consideration should be given to the possible effects of a positive result.

Bearing in mind that symptoms do not necessarily appear, a positive result may lead to worry and distress. If siblings are found to have the genetic markers for the disease, the threat of the disease may weigh upon them or/and their families even though they may never develop symptoms. In addition treatment may not be available to them before evidence of the disease shows and they may encounter problems with insurance, job applications etc.

If siblings are found to be carriers, their future in terms of marriage and having children may come under consideration. This is discussed more fully in Note 3 below.

Other relatives: the chances of other relatives having the disease are smaller. Testing may identify carriers and non-symptomatic relatives with the genetic markers for Gauchers disease but unless symptoms are apparent, screening may be considered unnecessary.

3. In couples where one partner is a sufferer or carrier, to test the other partner in order to advise on whether their child will have the disease, be a carrier or will not have the disease.

If a partner has the disease, has the genetic markers for the disease or is a carrier, he or she may wish to have the other partner tested to see whether they have the disease (or the genetic markers for the disease but without any symptoms) or whether they are a carrier, before they proceed to get married or have children. The implications of this must be considered prior to testing.

If the results comes back as negative for the mutations tested, the couple may have some assurance that any child will only be a carrier and may not even be that but there will be a slight possibility that the partner carries one of the rarer mutations which has not been tested for.

However if the other partner's result is positive, counselling should have included:

In Types 2 and 3, the incidence is so rare that discovery usually only takes place once a child has already been born with the disorder. In subsequent pregnancies, the fetus can be tested early in pregnancy. Otherwise if someone is found to be a carrier of Types 2 or 3, the chances of the other partner also being a carrier is extremely rare but screening can be obtained.

In Type 1, if both parents have Gauchers disease, the child must inherit the disease or the genetic markers for the disease. It is possible that one parent has the disease and the other partner also has the genetic markers for it but with no symptoms. Therefore the child may develop the disease or alternatively may not show any symptoms during its lifetime.

If one parent has the disease and the other is a carrier, in each pregnancy there is a 50:50 chance of the child inheriting the disease. The child may not have the disease as severely as the parent but there is a possibility of it being more severely affected depending on the genotype of the other parent. Symptoms vary considerably even among relatives who have inherited the same gene mutations.

If both parents are carriers, there is a one in four chance in each pregnancy that the child will have the disease or the genetic markers for it. Again it partly depends on the genotype of each parent on whether the affected child will have mild or severe disease (or even show any symptoms at all).

Counselling can be obtained to discuss the mutation (genotype) and the expected severity of the disease in Type 1 couples although currently prognosis on the severity of one of the most common genotypes in the UK is difficult as the symptoms can vary so widely.

The following should be considered by Type 1 couples:

4. In the population, to discover undiagnosed sufferers or those with genetic markers for the disease, to discover carriers and to aid research into the prevalence and severity of the disease and the carrier ratio.

In the general population, the screening of undiagnosed people who have the disease, or have genetic markers for it, and those who are carriers, is highly unlikely to occur because of the rarity of the condition. Excluding the Ashkenazi Jewish population, only 590 out of 59 million people in the UK are estimated to have genetic markers for the disease of whom just 235 will have symptoms. It is extremely doubtful whether the NHS would have the resources or the inclination to screen the general population and the Gauchers Association feels that the money would be better spent on informing the medical profession about the condition and treating existing sufferers.

The Ashkenazi population in the UK numbers approximately 300,000 of whom about 355 are thought to have inherited genetic markers for the disease although only about 90 will have symptoms. It is questionable whether healthy people in the Ashkenazi community should be screened to see if they have a condition which is unlikely to surface (1 in 3,400), which is not fatal and for which there is now a treatment once symptoms occur.

Information describing the disease and its symptoms should continue to be circulated so that should symptoms show, both families and their doctors can recognise and check whether they are indeed caused by Gauchers disease.

However to advise healthy individuals that they have a predisposition to a condition even though they may never show symptoms is not, in the Association's view, desirable. The same principle applies to the detection of carriers. The distress and possible future inconvenience this may cause the person tested and their family could far outweigh any benefit to the few who will develop the disease and who should be identified by well informed doctors if symptoms occur.

The desirability of providing medical treatment to apparently healthy people who have genetic markers for the disease but may never show symptoms is questionable and certainly not practical currently.

Research Any investigations involving human samples or tissue, even a population study, requires ethical permission which is determined by independent Ethical Committees.

Anonymous screening within the general population may help researchers verify existing statistics. However the Association feels that the emphasis on research should be to help sufferers, not solely for obtaining statistical information.

Screening to seek out genotypes and their severity should evolve from existing patients, rather than seeking out non-symptomatic individuals.

The carrier status amongst Ashkenazi Jews has been published by Prof Beutler: 1 in 11 are carriers.


Return to contents page
Screening for Gauchers disease
Incidence of Gauchers disease

Sources: Prof E Beutler, Prof T Cox, Dr I Ellis, Prof A Zimran, Genzyme Therapeutics, 'Living with Gaucher disease' brochure.

We would like to thank Prof T Cox, Dr A Metha, Dr A Vellodi, Dr E Wraith, Nurse L Burnett, Dr A Cooper, Prof B Winchester, Dr E Young for their comments on this revised paper.

© Gauchers Association 1993-1999. Revised February 1999. Minor clarification April 2004.