Metachromatic Leukodystrophy: Newborn Screening and Sibling Testing - Family and Expert Perspectives

This webinar brings together a family perspective and clinical/public-health expertise to make the case for newborn screening in metachromatic leukodystrophy (MLD), a fatal genetic neurodegenerative disorder caused by biallelic variants in the ARSA gene. Ally Wallace opens with her family's experience: a two-year diagnostic journey for her daughter Nala, whose early motor symptoms were repeatedly attributed to less serious causes before an emergency MRI led to a diagnosis of MLD too late for treatment, and the subsequent sibling testing that identified MLD in her younger daughter Teddy early enough for pre-symptomatic gene therapy.

Prof. Eklund then reviews the clinical rationale for screening: MLD's four age-defined subtypes (late infantile, early juvenile, late juvenile, and adult), the narrow treatment eligibility window (pre-symptomatic or early symptomatic disease only), and the outcome data showing that patients treated pre-symptomatically do substantially better than those treated after symptom onset. He outlines the three-tier screening pathway (sulfatide measurement, ARSA enzyme activity, and genetic confirmation) and the current landscape of pilot and national screening programs across Europe.

Dr. Oberg closes with a detailed account of Norway's implementation of the world's first nationwide MLD newborn screening program in January 2025, including method validation, real-world performance data (no false positives or gray-zone cases in the first year), cost-effectiveness, and the clinical pathway from a positive screen to gene therapy at Skåne University Hospital in Lund. The session ends with a panel discussion covering false-positive risk, the IQ-based treatment eligibility criterion for early juvenile MLD, and the policy and funding barriers to wider adoption of newborn screening.