Neonatal screening for inherited metabolic disorders

17 May 2005

Inborn errors of metabolism are a group of rare genetic disorders that, if untreated, can cause severely adverse clinical outcomes including irreversible mental retardation, physical disability and even death in affected babies. It is therefore extremely important to detect and accurately diagnose these disorders as soon as possible after birth. One of the best known examples of these diseases is phenylketonuria (PKU), an autosomal recessive disorder caused by mutation of the gene for a key enzyme involved in phenylalanine metabolism. In children with PKU, the levels of phenylalanine in the body build up to toxic levels, causing mental retardation and organ damage. However, early diagnosis and exclusion of phenylalanine from the diet allows affected babies to grow into normal, healthy adults.

A recent Health Technology Assessment report [Pandor A et al. (2004) Health Technol Assess. 8, 1-121] reviews the clinical efficacy and cost-effectiveness of neonatal screening for these inherited metabolic disorders using tandem mass spectrometry. Screening for inborn errors of metabolism involves measurement of the levels of specific metabolites present in the dried blood-spot specimens routinely collected from newborn babies. The presence of abnormal levels of certain metabolites (eg. amino acids and acylcarnitines) suggests the presence of particular metabolic disorders. Tandem MS (also called MS/MS) is a technique that has been shown to be suitable for the reliable detection of inborn errors of metabolism including PKU; it is highly accurate and able to measure multiple compounds simultaneously.

The review updated earlier HTA reports by means of a systematic review of research on tandem MS for newborn screening published since 1995, supplemented by a review of literature and a modelling exercise on the economics of tandem MS for neonatal screening in the UK. Evidence was mostly derived from studies of neonatal screening programmes using tandem MS in Australia, Germany and the USA, showing the technique to be rapid, highly sensitive (90

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