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A 30-minute webinar with Dr Lucia Laugwitz (University of Tübingen) updating the case for newborn screening in metachromatic leukodystrophy (MLD). A sibling case shows how pre-symptomatic identification opened access to gene therapy, and she reviews screening methods, biomarkers and their limits. For paediatricians and metabolic teams.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by arylsulfatase A (ARSA) deficiency, with sulfatide accumulation and CNS demyelination. Dr Lucia Laugwitz opens with a boy diagnosed at seven, whose early cognitive and behavioural symptoms were misattributed to ADHD until an IQ decline and abnormal MRI prompted testing; his asymptomatic younger sister, found to carry the same ARSA mutations, was diagnosed pre-symptomatically and became the first child in Tübingen to receive gene therapy for MLD. She emphasises the 'window of opportunity' before neurodegeneration, when both gene therapy and stem-cell transplantation work best, and sets out the rationale for newborn screening: a two-tier strategy testing dried blood spots for sulfatides and ARSA activity, followed by genetic confirmation, to separate true MLD from pseudodeficiency and carriers — while acknowledging technical limits and the need for better thresholds to reduce false positives. Biomarkers such as neurofilament light chain and N-acetylaspartate help with monitoring but are not sensitive enough to predict onset in newborns, and MRI, MRS and neurophysiology are useful for surveillance rather than early detection. She calls for international consensus on managing screen-positive newborns, notes a European project developing shared protocols, and stresses that screening and intervention should begin as soon as one child in a family is diagnosed.
After viewing this webinar, participants will be able to:
Juvenile MLD can begin with cognitive and behavioural changes — inattention, falling school performance, behavioural difficulties — before clear neurological signs, so it is easily misattributed to ADHD or a learning disorder. In the case presented, MLD was only considered after an IQ decline and abnormal MRI.
A two-tier approach: first test dried blood spots for sulfatides and arylsulfatase A activity, then confirm with genetic sequencing. This helps separate true MLD from pseudodeficiency and carriers, though thresholds still need refining to reduce false positives.
Not reliably. Biomarkers such as neurofilament light chain and N-acetylaspartate are useful for monitoring disease, but are not sensitive enough to predict onset in newborns; MRI, MRS and neurophysiology likewise help with surveillance more than early detection.
Screening and, where indicated, intervention should begin for siblings as soon as one child is diagnosed, because pre-symptomatic identification opens access to gene therapy or transplantation while they still work best.
This content is intended for healthcare professionals only. The views expressed are those of the presenters and do not necessarily reflect those of Excellence in Pediatrics; their inclusion does not imply endorsement. The content is provided for educational purposes only and does not constitute medical advice or replace independent clinical judgement.