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Detection of inborn errors of metabolism in the newborn
  1. A Chakrapani,
  2. M A Cleary,
  3. J E Wraith
  1. Willink Biochemical Genetics Unit, Manchester M27 4HA, UK
  1. Dr Clearymaureen{at}

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It is important for paediatricians and neonatologists to keep in mind inborn errors of metabolism (IEMs) as a cause of illness in the neonatal period, as many disorders are treatable and, in most cases, successful outcome is dependent on a rapid diagnosis and early instigation of therapy. Even with untreatable disorders, it is important to establish the diagnosis in the index case in order to allow prenatal diagnosis in subsequent pregnancies. In desperately sick neonates for whom no diagnosis is readily available, IEMs are near the top of the list of differential diagnoses.

IEMs can present in the newborn in a variety of ways. Typically, an IEM is suspected as a result of a suggestive combination of acute clinical symptoms without any prior warning. However, sometimes non-specific clues exist, such as a previous unexplained neonatal death and, in some families, the risk of an IEM is already highlighted by the presence of a previously affected child. IEMs may be detected through the newborn screening programme, though at present phenylketonuria is the only disorder for which mass screening is accepted in the UK. Some IEMs result in dysmorphism, and the investigation of these cases is not complete without considering metabolic causes. Finally, disorders that normally manifest in older children may sometimes cause abnormalities in the newborn period.

Pathogenesis of IEMs—“placental protection”

Like all genetic disorders, IEMs are present from conception, and most defective enzymes are active in fetal life. Nevertheless, most conditions have no adverse consequences on the fetus, as the placenta provides an effective dialysis system for the removal of toxic metabolites. Thus most babies with an IEM are born in good condition and of normal birth weight. Some IEMs, such as galactosaemia, manifest only after the substrate for the deficient enzyme becomes available in the form of feeds. There are some exceptions to …

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