Galactosemia Screening with Low False-Positive Recall Rate: The Swedish Experience

Abstract

Newborn screening was implemented in the 1960s with screening for phenylketonuria (PKU). In the same decade, it became possible to screen for classical galactosemia, a rare autosomal recessive inherited disorder, which is potentially life threatening if not treated. While newborn screening for PKU has become almost universal, galactosemia is included only in a minority of European newborn screening programs. The major arguments why galactosemia is excluded from newborn screening programs are that the disease can be diagnosed clinically, there is a high rate of false positives and long-term complications are common despite early diagnosis.

Here, we report how we have decreased the number of false-positive galactosemia recalls to less than 0.01%, using a two-tier test strategy. All samples are tested with the Beutler blood spot test, a method that measures galactose-1-phosphate uridyltransferase activity. Samples with less than ≤15% activity are tested for galactose with a galactose dehydrogenase test (the rapid GAL-DH test), which catalyzes the oxidation of galactose and the reduction of NAD⁺ to NADH that is estimated visually by fluorescence under UV-light. Both tests are semiquantitative.

With this strategy, screening for galactosemia is inexpensive, does not demand a heavy workload, and has a low false-positive re-call rate. The incidence of classical galactosemia in Sweden is 1/100,000, which is lower than the reported incidence in other European countries. Despite this, newborn screening for galactosemia has never been questioned.

Concise sentence: Screening for galactosemia using well-established methods to reduce the false-positive rate.

Competing interests: None declared.

References to Electronic Databases

OMIM disorder: http://www.ncbi.nlm.nih.gov/omim

Enzyme Commission (EC) number: http://www.chem.qmul.ac.uk/iubmb/enzyme