Appropriateness of newborn screening for classic galactosaemia: a systematic review

J Inherit Metab Dis. 2016 Sep;39(5):633-649. doi: 10.1007/s10545-016-9936-y. Epub 2016 Apr 26.


Currently, there is no universal agreement on galactosaemia screening, fundamentally because of the risk-benefit uncertainties. We conducted two exhaustive systematic searches in the main electronic databases (PubMed, Embase, Cochrane, etc.) to recover relevant information about the disease and screening test/s in order to support decision making in Spain. All of the 45 studies identified that covered disease issues were retrospective case series or cross-sectional analysis (level-4 evidence). Studies consistently found that the majority of patients presented characteristic symptomatology before diagnosis. Long term disabilities were not significantly correlated with age of diagnosis, onset of dietary restriction or strict diet compliance. The five studies that provided accuracy data used different cut-off points and verification tests, and thus differed in their definitions of a positive case (level-3b evidence). The estimated sensitivity was 100 % and the specificity 99.9 %. The false-positive rate ranged from 0.0005 % to 0.25 %, and the PPV from 0 % to 64.3 %. The comparative clinical effectiveness in relation to not screening or implementation of other programs is unknown. In summary, existing evidence remains insufficient to establish the appropriateness of newborn screening for galactosaemia screening, although health benefits could be expected if early diagnosis and treatment is achieved. If screening is implemented in Spain, it would be important that a pilot programme be implemented to assess false positive rate and ensure that early diagnosis is not delayed.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Cost-Benefit Analysis
  • Cross-Sectional Studies
  • Galactosemias / diagnosis*
  • Humans
  • Infant, Newborn
  • Neonatal Screening / methods
  • Retrospective Studies
  • Sensitivity and Specificity