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In this session, Dr. Caroline Sevin, a pediatric neurologist and Head of the Reference Center for Leukodystrophies in Paris, addresses the early identification and management of rare diseases in clinical practice, with a particular focus on Metachromatic Leukodystrophy (MLD). The presentation emphasizes the importance of recognizing rare diseases like MLD during routine pediatric care and the urgent need for early diagnosis in the context of new therapeutic options.
MLD is a lysosomal storage disorder caused by a deficiency in the arylsulfatase A enzyme, resulting in the accumulation of sulfatides and subsequent demyelination in the central and peripheral nervous systems. Dr. Sevin explains that early-onset forms of the disease progress rapidly and are often beyond the window of treatment by the time symptoms are recognized. Late-onset forms are more variable and slower to progress but still require early diagnosis to benefit from potential therapies.
Dr. Sevin outlines three distinct disease phases: normal development, stagnation, and regression. She underscores that the key to intervention lies in identifying the disease at the stagnation phase—before irreversible neurodegeneration has occurred. The presentation includes detailed guidance on red flags, such as unexplained delays in walking, toe-walking, balance issues, and sudden school performance decline. Strabismus, while non-specific, is also highlighted as a possible early symptom.
The session also shares findings from a retrospective French study of 80 patients with MLD, which showed that diagnosis is frequently delayed by an average of 12 months—even when parents raise early concerns. Many children, especially those with the late infantile form, never walk normally, yet their diagnosis is often missed or postponed.
Dr. Sevin explains the mechanics and potential of ex vivo gene therapy, which involves correcting a patient’s own stem cells in the lab and reintroducing them after myeloablation. The treatment has shown promising results, especially in pre-symptomatic patients, but requires very early intervention. She stresses the importance of family screening and advocates for the introduction of newborn screening programs.
The webinar concludes with a Q&A addressing practical diagnostic strategies in low-resource settings, the role of MRI, and differential diagnoses such as adrenoleukodystrophy. Clinicians are encouraged to maintain vigilance, listen closely to caregiver concerns, and act quickly when developmental regression or stagnation is suspected.