Report of the first Eurogentest Best Practice meeting of National Representatives of EU25

The aim of the meeting was to review best practice in Biochemical Genetic Testing including quality assurance (QA). Needs and deficits in Europe were identified and moves towards producing guidelines for Biochemical Genetic Testing and QA were initiated.  

Best practice in Biochemical Genetic Testing

Lectures on the state of the art for the following aspects of Biochemical Genetic Testing were presented. 

QA for Biochemical Genetic Testing in general: Leo Spaapen, Maastricht

Best practice for analysis and QA for various groups of metabolites 

• amino acids: Leo Spaapen, Maastrict (for  Brian Fowler, Basel)
• organic acids: Jim Bonham, Sheffield
• acyl carnitines: Charles Turner, London
• purines and pyrimidines: Jorgen Bierau, Maastricht
• diagnostic proficiency schemes: Christine Saban, Lyon
• general aspects of diagnostic guidelines: Jim Bonham, Sheffield
  (Presentations are available as Powerpoint files)

Biochemical Genetic Testing in the EU: strengths and weaknesses

Prior to the meeting all participants had been requested to complete a questionnaire aimed at surveying strengths and weaknesses of Biochemical Genetic Testing in the individual countries.

Questions included:  

•         the population size
•          the number of births / year
•          the disorders tested for and number of centres for newborn screening
•          the number of diagnostic laboratories performing Biochemical Genetic Testing
•          limitations to testing e.g. restricted funding
•          the spectrum of disorders covered
•          whether labs participate in external quality control
•          whether labs are accredited
•          whether any national training programmes are in place
•          whether succession planning for staff is in place
•          the number of medical centres for IEM
•          whether there are any IEM(s) with unusual incidence in individual countries.

It must be recognised that due to different recording systems and sometimes lack of structured provision of services the information provided cannot be completely accurate. Nevertheless the information afforded by the questionnaires served as a valuable basis for work during the meeting. Questionnaires were completed by 24 National Representatives from the EC countries. A National representative from Malta had not been identified.
The questionnaire information is summarised as follows:  

Population size 

The very wide variation in population within the total population of 445 million (381 million EU15 and 74 million new member countries) renders design of guidelines for individual countries extremely difficult.
Thus 3 countries have a population < 1 million, 6 countries 1-5 million, 6 between 6 – 10 million, 4 between 11 – 20 million, 2 between 20 – 50 million and 4 > 50 million.

Number of births / year

The number of births / year ranges from 5’600 to 754’000 with an average of approx. 190’000  

Newborn Screening: disorders tested for and number of centres

The highest number of disorders are tested for by newborn screening in Austria, Portugal and Germany, with a number of 27, 15 and 12, respectively.
In other countries the number of disorders tested is between 1 and 6 with slightly more disorders tested in the old EC countries in comparison to the new EC members. Finland only screens for hypothyroidism.
In all 24 EC countries there are 150 Centres for Newborn Screening. 130 centres are in the old and 20 in the new member countries.
The number of centres for screening related to population is shown in Figure 1.
It must be noted that for those countries with more than one centre the values shown are only averages and there may be a large variation in numbers screened in each centre.

Figure 1: * countries with one centre, ** only Hypothyroidism

Number of Diagnostic laboratories performing Biochemical Genetic Testing 

In total there are 162 diagnostic labs performing Biochemical Genetic Testing , 136 labs in the old member and 26 in the new member countries. (excluding France for which data is unavailable).
On average, one Biochemical Genetic Testing laboratory covers a population of 2.8 million. 
The number of centres related to population for individual countries is shown in Figure 2.  

Figure 2: * not available, ** no centre 

Number of medical centres for IEM 

Overall there are 147 medical centres known to be active in the field of IEM, 126 are in the old EC countries and 21 are in the new member countries. The average size of population per one centre is 2.9 million in old member 3.4 million in new member countries.

Limitations to Biochemical Genetic Testing  

Several main reasons were given as the reason for limitation of Biochemical Genetic Testing

• Funding restrictions are the principal limitation in 18 countries 
• Lack of specialised staff in IEM is a factor in 9 countries
• the size of population size sets the limit for 4 countries
• lack of QC schemes for some tests available 

Funding problems seem to be a factor both in old and new EC countries with funding limitations reported in 8 of 9 from new member and 12 of 13 from old member countries.

The spectrum of disorders covered and estimated case numbers

To answer this question data was sought in the form of this table 

Spectrum of tests available	Nationally	Internat.	Estimate* number test /year	Estimate* number cases /year
Amino acids	22/24	4/24
Organic acids	19/24	6/24
Carbohydrate Metabolism	18/24	8/24
Fatty  acid oxidation	16/24	10/24
Respiratory Chain	14/24	6/24
Mucopoly-saccharidoses	20/24	6/24
Sphingo-lipidoses	14/24	8/24
Purines, Pyrimidines	15/24	9/24
Peroxisomal Disorders	16/24	8/24
Creatine synthesis disorders	9/24	11/24
Congenital disorders of Glycosylation	14/24	8/24

Testing for amino acids, organic acids, carbohydrates and mucopolysaccharides is available in most countries (19-23/24) National availability for other tests is less complete with, for example, creatine synthesis disorders testing only available in 10 countries. Most large countries provide all tests nationally while smaller countries clearly need to obtain some types of Biochemical Genetic Testing abroad. 
Regarding sample load and cases found it is clear from results obtained in this survey as well as previous experience that it is extremely difficult to obtain comprehensive, accurate data on this question, particularly the numbers of cases detected. Problems relate to undesirability to share data and confusion between new cases and already diagnosed ones but the main deficit is usually a lack of a complete diagnostic register. No data was given by 9 countries and for these and even for those countries for which estimates were provided it is necessary to carry out more research to obtain meaningful estimates of case loads on a European-wide basis. 

Participation in External Quality Control 

In general laboratories from most countries perform a full or partial program of EQA although within a country participation may be incomplete. Thus 16 countries report participation of all labs and 8 report participation of some labs (ie. Belgium, Czech Republic, France, Finland, Germany, Poland, Slovakia and Spain). Overall there is no major difference between old and new member countries. This observation emphasises that there is still a need to expand EQA.

Accreditation 

In most countries there are no accredited laboratories. In 10 countries all or some laboratories are accredited. In the U.K. 15 of the 16 labs are accredited by CPA. The types of accreditation are not always the same with accreditation of tests in Estonia, of prenatal diagnosis (metabolites in amniotic fluid and molecular biology) but only for a particular person and not the lab in France.

Training 

Training programmes both in old and new member countries appear to be poorly developed. Thus 4 out of 14 and 4 out of 9 have a training programme in old and new member countries, respectively.
This is clearly an important limitation to Biochemical Genetic Testing as mentioned above.

Succession planning 

Planning for the succession of staff is in place in just 9 countries but even in those countries it is not always complete.

The occurrence particular IEMs with unusual incidence

An unusually high or low incidence of a particular inherited IEM may influence the type of Biochemical Genetic Testing in a country.  
An unusual incidence of an IEM was reported in 10 out of 24 countries as follows:

• Austria: MPS IVB, CDG, propionic acidaemia, glutaric aciduria
• Cyprus: one village has a carrier frequency for GM1 gangliosidosis of 1:12 and Sandhoff disease has a carrier frequency is 1:7 in Maronite community (<1% of the population)
• Estonia: very low incidence of MCAD deficiency of 1:193 000
• Finland: lysinuric protein intolerance, hyperornithinemia with gyrate atrophy, aspartylglucosaminuria, Salla disease, very low incidence of PKU (zero among original Finns)
• Greece: Sanfilippo typeB 
• Ireland: PKU, Galactosaemia, GA1, ? Resp. chain defects, Cystic fibrosis
• Netherlands: several very rare diseases e.g. Cog-7 deficiency
• Poland: low incidence of MCAD, high incidence of LCHAD, high prevalence of the 841delCT mutation of the SURF1 gene
• Slovakia: alkcaptonuria with the world-wide highest incidence of 1 in 19000, Smith-Lemli- Opitz syndrome with  asuggested incidence of 1 in 20000,
• Slovenia: low number of galactosemia patients

Last changed: 2008-02-04