Current newborn screening programmes; successes, pitfalls and lessons learned.

J.V Leonard, Institute of Child Health, London.

Only some aspects of current screening programmes for inborn errors of metabolism will be reviewed, concentrating primarily on those in the UK and the Republic of Ireland.

Neonatal screening for phenylketonuria became universal in the 1970s and overall it has been a considerable success in preventing severe mental retardation. However the mean IQ of the treated patients remained slightly below that the general population. Missed cases are rare and almost always the result of a failure of the screening process rather than a true false-negative.

The screening for classical homocystinuria is routine in the Republic of Ireland as the birth incidence is relatively high (~1:65,000). The screening process uses a proxy marker, plasma methionine concentration but up to 20% of cases are missed. In genetically more heterogeneous populations this would mean that many patients could be missed. Nevertheless dietary treatment can be started a young age and with good compliance the outcome of the screened patients is good.

Maple syrup urine disease is a very rare disorder in most populations but is also more common in the Republic of Ireland. This disorder often presents as a sub-acute encephalopathy in the newborn period. However, because there are no obvious clues that it is a metabolic disorder, the diagnosis is frequently seriously delayed. As result of the prognosis for these patients is poor and the burden of the disease can be severe. With early intervention the outlook would be much improved. It is would be necessary to review on what day should be the screening sample be taken and the result reported.

Most patients with galactosaemia present in the newborn period with a serious illness. The response to the galactose free diet is often dramatic with rapid improvement. However the long-term outlook has been disappointing. There is no evidence that early detection improves this. Although the screening is still widespread in the USA and Germany, it is now been largely abandoned in the UK. The screening process also has the disadvantage that patients with mild disease who need little or no treatment are detected. It is important that the phenotype and the natural history should be well understood.

Long-term follow-up is essential and wherever possible control groups should be incorporated. There should be guidelines about the management of mild cases and clear decisions also need to be taken about the day of screening and reporting.

Families now have easy access to more information as well as international comparisons. Furthermore society's expectations are that a child will grow up healthy and perhaps controversially this may mean that decisions about screening for rare disorders will need to be re-examined.