The universal screening of phenylketonuria and hypothyroidism are good
examples of this concept.
Those are diseases that affect approximately 1 out of 10,000 neonates,
Note : the tests will detect hyperphenylalaninemia but not its cause: it
could be a true enzymatic deficiency or transitory, (prematurity
manifested by hyperphenylalaninemia and hypertyrosinemia or excess
nutritional phe intake). The diagnosis must be confirmed by more precise
Treatment : substitution by tryptophane and serotonine, close follow up,
genetic counselling and psychological aid.
In most programs TSH is measured on filter papers. If TSH is elevated
the diagnosis must be confirmed with plasma measurements ( TSH, free T4,
Initially 10µg/kg de L Thyroxine with periodical controls of thyroid
function every 3 months until one year of age then every 6 months until
three years of age and thereafter every year.
An overview of measures taken throughout the world confirms that
neonatal screening was initiated in several countries in different ways
and in most cases in relation to the populations more at risk to develop
a metabolic disease like phenylketonuria hypothyroidism and / or cystic
fibrosis (mucoviscidosis). This is particularly true for blood dyscrasias such as sickle cell
anemia and thalassemia, two diseases that are more frequent in the
Mediterranean countries, Africa and Asia. Tyrosinemia is frequent in
Finland and the Quebec Saguenay region. This implies that specific
screening tests are developed according to the mutant gene frequencies
found in certain populations that often live in isolates. Neonatal screening programs have been adopted by several
countries. For instance neonatal screening for phenylketonuria and
hypothyroidism are current practice in several countries of North
America, Europe, in Japan New Zeland, Australia, Israel and more
recently in China and South America (WB Hanley, personal communication).
TANDEM MASS SPECTROMETRY
The development of tandem mass spectrometry (MS/MS) has allowed in
recent years the detection, confirmation of diagnosis and the follow up
of newborns affected with phenylketonuria, hepatorenal tyrosinemia and
MCAD (medium-chain acyl co-enzyme A dehydrogenase) deficiency and will
probably be a screening tool for several metabolic disorders such as
organic acidurias and urea cycle defects.
Approximately 2 to 40 metabolic diseases can be detected in the neonatal
The majority are in need of medical intervention, some will need a close
It is generally accepted that neonatal screening can apply to non
metabolic diseases like hearing deficits.
A number of health services have initiated hearing evaluation by
otoacoustic emissions in the neonatal period for newborns aged from 30
months of gestation to full term.
This neonatal screening for hearing has the same goal as the screening
programs for cystic fibrosis and Duchenne muscular dystrophy(DMD) that
is to minimize secondary effects of evolutive diseases.
In cystic fibrosis a diagnosis made in the early infancy allows the
introduction of a special diet: studies have shown an improvement in the
general health and growth of the patient.
The incidence of cystic fibrosis being between 1 in 2000 to 1 in 4000
births, this screening program has been adopted by several health
authorities. A family study and genetic counselling are applied.
In muscular dystrophy the advantage of an early treatment does not seem
as efficient since the age of onset of the disease is variable and often
the motor symptomatology is non specific and may be similar to certain
orthopedic disorders. In the future an improved detection method,
reducing positive and negative results, would allow to reconsider the
indication to screen for DMD in the neonatal period.
The screening for the immunodeficiency virus (HIV) in the neonate is
controversial on ethic and clinical grounds. Although the early
treatment of the newborn who is a virus carrier seems to prevent the
acquired immunodeficiency syndrome several groups contest the universal
neonatal screening for the virus since there is an elevated risk of
individual and ethnic discrimination.
Following biochemical, enzymatic and molecular studies that confirm the
diagnosis a treatment is applied :
As shown in phenylcetonuria the alimentary restrictions and special
foods will prevent overloading of catabolites deleterious to the child
development. Protein or specific amino acid restrictions are indicated
in most metabolic diseases. Food banks are generally under the state
supervision and are responsible for the availability of special foods to
The introduction of a gene in a patient, with an appropriate vector to
correct an abnormal metabolism. This domain is under sustained research
particularly in cancerology and in the study of hereditary degenerative
One may identify among hereditary diseases those for which the
symptomatology is absent in the neonatal period but appears later during
infancy or in adolescence and those that have a true late age of onset
during adulthood. Among metabolic diseases with late manifestations one
notes the intermittent leucinosis that has a residual enzymatic activity
enough to delay the appearance of symptoms if there is no increase in
intake of food containing branched chain aminoacids. An infectious
disease in the child may trigger typical manifestations of this disease
commonly called maple syrup urine disease because of the urine odour.
Access to neonatal screening in a modern society is primordial. However
for economical reasons or expertise disponibility all newborns will not
be tested. The number of diagnosable diseases has increased in recent
years and this stresses the importance at least to identify populations
that are more at risk to develop a disease.
Parents consent for the screening test is not obligatory in all states.
There are a number of policies regarding the access to the test.
According to countries and regions a neonatal screening test informed
consent may be:
ii. mandatory with option to refuse the test or
If the screening test is positive a genetic counselling is offered to
parents in view of a future pregnancy and, if they agree, to other
family members identified as individuals at risk. A prenatal diagnosis
can also be offered if a diagnosis can be reached by studying amniotic
fluid or cells.
Who will assume the development cost of these programs ? In general the
state is responsible and must also see to the follow up of patients who
had a positive screening test, to the long or short term appropriate
treatment, and the genetic counselling to be offered to the parents of
the positively screened individuals.
The institution or other accredited organism is also responsible to the
development of screening techniques and their validation. The use of
tandem mass spectrometry leads to new therapeutic approaches, increase
the survival of children for whom a diagnosis is made early who will
eventually rely on the take over by adult medicine services.
Ethics committees and the scientific community may be invited to study
the merit of new disease screening methods developed and proposed by
research groups: it is then the duty of ethic committee members to
formulate an advice in consultation with the population on the
pertinence of introducing new screening tests.
Dallaire L, Huret JL
Atlas of Genetics and Cytogenetics in Oncology and Haematology 2005-05-01
Online version: http://atlasgeneticsoncology.org/teaching/30056/neonatal-screening