ADVANCES IN
NEWBORN SCREENING
Shih VE
Massachusetts General Hospital, Boston, USA
Inborn errors of metabolism are a group of
metabolic disorders, usually autosomal recessively inherited. Common
clinical manifestations include developmental delay and acute metabolic
decompensation. Acute decompensation includes hyperammonemia, ketosis, or
hypoglycemia. Sudden death has been reported. With treatment, especially
early treatment, the outcome can be greatly improved. The concept of
newborn screening was pioneered by Dr. Robert Guthrie in 1965. He first
developed a bacterial inhibition assay to detect phenylketonuria (PKU)
followed later by assays for several other amino acid disorders. In the
following two decades, this technique and fluorometric methods were used to
develop additional assays for the detection of several other amino acid
metabolic disorders. However, there was clearly a need for a technique to
screen for the many organic acidurias and fatty acid oxidation defects that
can cause life-threatening illness. Early treatment can prevent brain
damage and save life in such patients. Tandem mass spectrometry (MS-MS) was
a new technique applied to medical use in the early 1990s. The development
of screening techniques using MS-MS have revolutionized newborn screening.
MS-MS is a quantitative, sensitive, reliable and cost effective way to
screen dried blood spots from a large number of infants. At least 35
disorders can be detected by a testing full panel of acylcarnitine and
amino acids. The prevalence of these disorders is between 1:4000 to 1:5000
in over 1 million neonates screened. Government sponsored pilot programs
and private laboratories throughout the world have recently expanded their
screening programs to include these disorders. Referral of infants detected
by screening to a metabolic clinic for evaluation and treatment is an
important aspect of the sucessful screening program.