Clinical and Developmental Outcomes After 50 Years of Newborn Bloodspot Screening for Classical Galactosaemia in the Republic of Ireland

Abstract

Classical Galactosaemia (CG) is an inborn error of carbohydrate metabolism. In untreated neonates, CG leads to a multi-organ toxicity with life-threatening symptoms. Newborn Screening for CG began in the Republic of Ireland in 1972. In Ireland, two forms of neonatal screening occur. High-risk infants are fed lactose-free/galactose-free formula until the result of their Beutler screening test on day 1. All other infants are fed as per parental preference and are screened on day three to five. While immediate or early implementation of a strict lactose-free diet together with medical interventions will usually address the acute medical complications, long-term complications are common. We reviewed retrospectively and anonymised the clinical outcomes of our CG cohort, derived from our hospital-based database. Patient demographic information, co-morbidities, developmental assessment results, and other relevant health indicators were analysed from birth to 18 years. Out of 217 patients, 95% of subjects were alive at 18 years of age. Common co-morbidities were speech and language difficulty (43.5%) and learning difficulty (25.5%). In this Irish cohort, Friedreich Ataxia is a genetically linked condition for a subgroup of CG individuals (7.9%). Our data demonstrate that while early diagnosis prevents mortality, it does not prevent developmental disorders, underpinning the neuro-developmental nature of CG. High-risk and routine newborn screening for CG have reduced the mortality rate of the disorder, and early medical and dietetic intervention is a success story. However, long-term medical and developmental challenges persist, and an early, proactive multidisciplinary approach may further mitigate the phenotype in CG patients diagnosed on NBS.

Keywords: carbohydrate metabolism; cataract; classical galactosaemia; galactose; neurocognitive outcomes; neuro‐development; newborn screening; outcomes.

FIGURE 1

Diagnostic pathway of the Classical Galactosaemia cohort in the Republic of Ireland. *Four patients had symptomatic testing in addition to NBSP while NBSP result was pending. CG: classical galactosaemia; HRS: high‐risk screening; NBS: standard newborn screening; NBSP: Newborn screening program; ROI: Republic of Ireland. Children with CG, Children without CG, Children in whom CG status is unknown.

FIGURE 2

Presence of acute intoxication symptoms at diagnosis in infants with classical galactosaemia. CG: classical galactosaemia; HRS: high‐risk screening; NBS: newborn screening.

FIGURE 3

Correlation heatmap showing Pearson correlation coefficients between numerical variables in the paediatric classical galactosaemia population. Standard diet: Breastmilk or cows‐milk infant formula pre‐diagnosis. CG: classical galactosaemia; HRS: high‐risk screening; LD: learning difficulty; NBS: newborn screening; SLD: speech and language difficulty.

FIGURE 4

Neurocognitive outcomes in children over 5 years old with classical galactosaemia. CG: classical galactosaemia; HRS: high risk screening; LD: learning difficulty; NBS: newborn screening; NS: No significance; SLD: speech and language difficulty.

FIGURE 5

Cataract prevalence throughout childhood in the paediatric classical galactosaemia population. Note: The diagnostic pathway was unknown for 2 children, and that only children for whom ophthalmic data was available are represented in this chart. NS: No significance.