NEWBORN SCREENING FOR HOMOCYSTINURIA - IRISH AND WORLD EXPERIENCE

Newborn screening for cystathionine beta-synthase deficiency (homocyst inuria; HCU) was started in the late 1960s using a bacterial inhibitio n assay (BIA). At least seven countries have either national or region al screening programmes; 12 programmes are known to have discontinued, The worldwide incidence of HCU is approximately 1 in 335,000 but vari es from 1:65,000 (Ireland) to 1:900,000 (Japan). Methodologies include the BIA, one-dimensional or thin-layer amino acid chromatography and, more recently, tandem mass spectrometry. The BIA diagnostic cut off c oncentration of blood methionine varies from 67 to 270 mu mol/l (10-40 mg/l) with a median of 135 mu mol/l (20 mg/l). In Ireland, 25 cases o f HCU from 19 families have been identified from 1.58 million newborn infants since 1971: 21 cases were detected through the screening progr amme. Of the four missed cases, three were breast-fed at the time of b lood collection and one was pyridoxine responsive. These findings were in broad agreement with the results from five other programmes, in wh ich approximately one in every five cases was missed by the screening programme. Early hospital discharge, low protein intake, high blood me thionine cut-off concentration and pyridoxine responsiveness were all identified as contributing to missed cases.