OBJECTIVES: Traditionally, neonates were screened for classical galactosaemia in 4 of the 5 jurisdictions in Australia creating inequitable access to early intervention. A push to nationally harmonise newborn bloodspot screening enabled the state of Victoria to proceed with implementation of screening for galactosaemia types 1 to 4 enzyme deficiency i.e. galactose 1-phosphate uridyl transferase (GALT-D), galactokinase (GALK-D), epimerase (GALE-D) and mutarotase (GALM-D) deficiencies. This also provided the opportunity to take a modern look at an old screening condition. METHODS: As part of the implementation of galactosaemia screening two studies were conducted. 1) Suitability study, where dried bloodspot (DBS) samples were analysed using Revvity test kits over a three-week period: first-tier total galactose (TGAL) quantification and second-tier GALT semi-quantitative analysis was performed using 3.2 mm DBS punches and a Genetic Screening Processor. 2) 18-month review study of performance based on the referrals made to the clinical team. RESULTS: The suitability study analysed 4,421 DBS samples, comprising 48.7 % female and 51.3 % male, with gestational ages 22-43 weeks to develop decision limits. TGAL concentrations ranged from 16 to 1,323 μmol/L, while GALT enzyme activity varied between 600 μmol/L for TGAL and <20 U/L for GALT. A total of 115,091 babies were screened during the 18-month review period and 13 were referred for clinical follow-up (i.e. screen positive); with one baby confirmed to have classical galactosaemia. CONCLUSIONS: The studies demonstrated that performance of the automated TGAL and GALT assays is robust for our neonatal population. However, attempting to formally include all four forms of galactosaemia as target conditions results in a lower TGAL cut-off and more false positives. With the need to consider balancing benefits vs. harms, we recommend that screening for galactosaemia due to GALE-D or GALM-D be changed to non-target conditions in the Australian NBS framework.
Wong et al. (Wed,) studied this question.