International Journal of Neonatal Screening

X-linked adrenoleukodystrophy (X-ALD) is the most common leukodystrophy and peroxisomal disorder. It was added to newborn screening (NBS) programs following its first implementation in New York in 2013. Since then, X-ALD screening has expanded rapidly, although important differences exist among programs. This systematic review aimed to evaluate the global implementation of NBS for X-ALD, including screening methodologies, screening performance, prevalence estimates, genetic findings, and clinical follow-up outcomes. A systematic search of PubMed and EMBASE identified 13 publications describing NBS programs conducted between 2013 and June 2026. All programs used C26:0-lysophosphatidylcholine (C26:0-LPC) as the primary biomarker, although substantial heterogeneity was observed in analytical methodologies, cut-off values, screening algorithms, and follow-up strategies. Positive predictive values ranged from 9.1% to 100%, while screening detection rates varied from 1:3118 to 1:51,081, reflecting differences in study design, screening population, sample size, and screening approaches. Variants of uncertain significance (VUS) accounted for 52.6% of individuals detected with classified ABCD1 variant findings, representing a major challenge for genetic counseling and clinical management. Most identified newborns were asymptomatic at diagnosis, supporting the role of NBS in enabling early surveillance for adrenal insufficiency and cerebral disease before irreversible manifestations occur. In addition, differences between universal and sex-specific screening strategies highlight ongoing clinical and ethical debates regarding the scope of X-ALD NBS. Overall, current evidence supports the feasibility of NBS for X-ALD and its ability to enable presymptomatic ascertainment and early clinical surveillance; however, greater harmonization of screening protocols, improved variant interpretation, and long-term outcome studies are needed to optimize program performance and clinical benefit.

Newborn screening (NBS) is an essential public health intervention for early detection and secondary prevention of inherited disorders in asymptomatic infants at birth. Advances in this field and the accessibility of new screening methods and therapies in the last decade have insurmountably surpassed Malaysia’s national NBS programme, which has stagnated. Currently, our mandatory nationwide routine screening is limited to only two conditions: glucose-6-phosphate dehydrogenase deficiency and congenital hypothyroidism. While services such as universal newborn hearing and critical congenital heart disease screening are available in many settings, most treatable genetic and metabolic disorders remain unscreened. Consequently, preventable morbidity and mortality, from inborn errors of immunity and metabolism, and genetic diseases persist. This position statement reviews the evidence for expanding the national NBS programme in Malaysia, arguing that a modernised, contemporary and pragmatic method is both clinically tenable and morally imperative. By embracing advancements for expanded NBS, Malaysia can safeguard children’s right to an open future, fulfil intergenerational justice, and ensure that no infant is left without the opportunity for life-saving care.

Communication of screen-positive newborn bloodspot screening (NBS) results is inherently challenging for both parents and HCPs. There is no internationally accepted gold-standard model, with heterogeneity in practice and with many jurisdictions reporting suboptimal parent and HCP experience. This service evaluation aimed to assess the model for communication of initial screen positive results for metabolic conditions through the Irish National Newborn Bloodspot Screening Programme (NNBSP). Under the current model, screen-positive results are communicated to parents by a healthcare professional (HCP) (usually over the phone) and follow-up is arranged through the maternity hospital of birth. The evaluation required engagement with three cohorts, comprising two parent cohorts (a True Positive (TP) cohort and a False Positive (FP) cohort) and one HCP cohort. A separate survey was designed for each cohort, informed by a review of the international literature and subject matter expertise. Overall, our evaluation found that the current model for communication of screen-positive results is acceptable to HCPs, the majority of whom regard communicating these results as an appropriate part of their role (61%) and feel confident doing so (68%). However, many parents reported that they did not receive key information, and 70% wanted more information at this first communication. Parents wanted clear, reassuring, and actionable information, including details of the suspected condition, next steps, and where to seek further support. HCPs wanted additional resources to support communication of screen-positive results, including guidelines, expert contacts, condition-specific information resources, and checklists. The findings of this evaluation will inform revisions of the current model, aimed at ensuring a better experience for parents and HCPs.