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Klinika Pediatrii, Instytut Matki i Dziecka,
Kasprzaka 17a, 01-211, Warszawa, Poland.
Inborn errors of metabolism, in spite
of their not very high incidence play more and more evident
role in the causes of infant's mortality and morbidity.
Therefore early diagnosis and early treatment becomes an
important issue in contemporary medicine. The criteria for
newborn mass screening, selective screening and supplementary
screening as well as the new technologies, among others
mass spectrometry, Tandem MS, were discussed.
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New South Wales Newborn Screening Programme,
the Children's Hospital at Westmead, Sydney, NSW, Australia.
BACKGROUND: The recent development
of electrospray tandem mass spectrometry makes it possible
to screen newborns for many rare inborn errors of metabolism,
but the efficacy and outcomes of screening remain unknown.
We examined the effect of the screening of newborns by tandem
mass spectrometry on the rates of diagnosis of 31 disorders.
METHODS: We compared the rates of detection of 31 inborn
errors affecting the metabolism of the urea cycle, amino
acids, and organic acids and fatty-acid oxidation among
362,000 newborns screened by tandem mass spectrometry over
a four-year period (April 1998 through March 2002) with
the rates in six preceding four-year birth cohorts in New
South Wales and the Australian Capital Territory, Australia,
where screening, diagnostic, and clinical services were
centralized. RESULTS: The overall prevalence of disorders
during the periods when clinical diagnosis was used did
not vary between 1982 and 1998. In the cohort screened with
tandem mass spectrometry, the prevalence of inborn errors,
excluding phenylketonuria, was 15.7 per 100,000 births (95
percent confidence interval, 11.9 to 20.4), as compared
with adjusted rates of 8.6 to 9.5 per 100,000 births in
the four preceding four-year cohorts. Of the 57 cases diagnosed
after the introduction of newborn screening, 15 were diagnosed
clinically; 7 of the 15 newborns had a normal result on
screening. The rate of detection was increased specifically
for medium-chain acyl-coenzyme A dehydrogenase deficiency
(P<0.001) and other disorders of fatty-acid oxidation
(P=0.007), as compared with the 16-year period before the
implementation of neonatal screening for these disorders.
CONCLUSIONS: More cases of inborn errors of metabolism are
diagnosed by screening with tandem mass spectrometry than
are diagnosed clinically. It is not yet clear which patients
with disorders diagnosed by such screening would have become
symptomatic if screening had not been performed.
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Department of Cardiological Sciences,
St George's Hospital Medical School, London.
OBJECTIVES. To establish a database
of literature and other evidence on neonatal screening programmes
and technologies for inborn errors of metabolism. To undertake
a systematic review of the data as a basis for evaluation
of newborn screening for inborn errors of metabolism. To
prepare an objective summary of the evidence on the appropriateness
and need for various existing and possible neonatal screening
programmes for inborn errors of metabolism in relation to
the natural history of these diseases. To identify gaps
in existing knowledge and make recommendations for required
primary research. To make recommendations for the future
development and organisation of neonatal screening for inborn
errors of metabolism in the UK. HOW THE RESEARCH WAS CONDUCTED.
There were three parts to the research. A systematic review
of the literature on inborn errors of metabolism, neonatal
screening programmes, new technologies for screening and
economic factors. Inclusion and exclusion criteria were
applied, and a working database of relevant papers was established.
All selected papers were read by two or three experts and
were critically appraised using a standard format. Seven
criteria for a screening programme, based on the principles
formulated by Wilson and Jungner (WHO, 1968), were used
to summarise the evidence. These were as follows. Clinically
and biochemically well-defined disorder. Known incidence
in populations relevant to the UK. Disorder associated with
significant morbidity or mortality. Effective treatment
available. Period before onset during which intervention
improves outcome. Ethical, safe, simple and robust screening
test. Cost-effectiveness of screening. A questionnaire which
was sent to all newborn screening laboratories in the UK.
Site visits to assess new methodologies for newborn screening.
The classical definition of an inborn error of metabolism
was used (i.e., a monogenic disease resulting in deficient
activity in a single enzyme in a pathway of intermediary
metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM.
Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all
the screening criteria and could be used as the 'gold standard'
against which to review other disorders despite significant
variation in methodologies, sample collection and timing
of screening and inadequacies in the infrastructure for
notification and continued care of identified patients.
Of the many disorders of organic acid and fatty acid metabolism,
a case can only be made for the introduction of newborn
screening for glutaric aciduria type 1 (GA1; estimated incidence
1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD)
deficiency (estimated incidence 1:8000-1:15,000). Therapeutic
advances for GA1 offer prevention of neurological damage
but further investigation is required into the costs and
benefits of screening for this disorder. MCAD deficiency
is simply and cheaply treatable, preventing possible early
death and neurological handicap. Neonatal screening for
these diseases is dependent upon the introduction of tandem
mass spectrometry (tandem MS). This screening could however
also simultaneously detect some other commonly-encountered
disorders of organic acid metabolism with a collective incidence
of 1:15,000.
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