Newborn screening in metachromatic leukodystrophy – European consensus-based recommendations on clinical management

Exploring the Cost-Effectiveness of Newborn Screening for Metachromatic Leukodystrophy (MLD) in the UK

“…Given that arsa-cel is only indicated for early-onset MLD, for the small proportion (10%) of late-onset MLD patients, additional inputs for lifetime costs and QALYs for treatment with allogeneic hematopoietic stem cell transplant (HSCT) or bone marrow transplant were obtained from the HSCT/BMT arm of the NICE HST7 appraisal of Strimvelis, another gene therapy approved for the treatment of ADA-SCID, as a proxy for MLD in the absence of any published cost-effectiveness data for adult-onset MLD [ 23 ]. Whilst late-onset patients would not be treated until sub-clinical evidence of disease was present [ 18 ], for the purposes of the modelling the long-term costs of HSCT have been applied assuming late-onset patients will receive HSCT as an infant. In the no-screening arm, for untreated patients it has been assumed that patients will experience normal health until onset of symptoms aged 16.…”

“…If treatment for MLD is administered prior to the onset of symptoms in screen-positive babies, it is imperative that the prediction of MLD subtypes in pre-symptomatic neonates is possible. European consensus-based recommendations on the clinical management of newborn screening in MLD strongly recommend predicting the age of symptom onset based on family history, genotype and ARSA enzyme activity [ 18 ]. In neonates without affected relatives, the prediction relies primarily on genotype–phenotype correlations as published in the literature and public databases.…”

“…The general rule is that a 0/0 genotype is most likely to be late infantile; and for 0/R and R/R mutations, EJ MLD is suspected if it is based on known mutations which have been shown to cause EJ-MLD, e.g., the mutation of the ARSA variant c.465+1G>A coupled with the second most frequent variant c.1283C>T, p.(Pro428Leu). Homozygosity for the c.1283C>T, p.(Pro428Leu) variant is associated with late-juvenile or adult onset [ 18 ].…”