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A 60-minute webinar with Dr Francesca Fumagalli (San Raffaele Hospital, Milan) and Dr Alejandra Darling (Hospital Sant Joan de Déu, Barcelona) on spotting the early signs of metachromatic leukodystrophy (MLD). Through videos and real cases they show the subtle, age-specific red flags — and the extra-neurological clues — that make the difference now that gene therapy exists. For paediatricians, paediatric neurologists and frontline clinicians.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by arylsulfatase A deficiency, in which sulfatide accumulation drives progressive demyelination of the central and peripheral nervous systems. Dr Francesca Fumagalli and Dr Alejandra Darling set out the earliest signs by age of onset: in the late-infantile form (onset below 30 months), developmental stagnation, hypotonia, ataxia, abnormal reflexes, retrocurved knees and toe-walking — with around half of children never walking independently; in the juvenile forms, behavioural change, a fall in school performance, clumsiness and fine-motor decline that are easily misread as inattention or a psychological problem. Because these signs are non-specific, diagnosis is delayed by months or years, and early brain MRI can be normal. Using illustrative cases — a two-sibling case in which delay excluded the older child from treatment while the younger was treated pre-symptomatically, and a case first mistaken for Guillain-Barré syndrome after a post-infective decline — the presenters stress that peripheral, central and behavioural involvement can be superimposed, that a sudden strabismus or gallbladder abnormality can precede neurological signs, and that biochemical tests (arylsulfatase A activity and sulfatides, including on dried blood spots) give an answer far faster than broad genetic panels. Their core message: act on developmental stagnation in young children and on new behavioural or coordination change in older ones, refer early, and remember that eligibility for gene therapy depends on catching MLD before irreversible decline.
After viewing this webinar, participants will be able to:
They differ by age. In late-infantile MLD (onset below 30 months): developmental stagnation after a normal start, hypotonia, ataxia, abnormal reflexes, toe-walking and retrocurved knees — and around half of children never walk independently. In juvenile MLD: behavioural change, a fall in school performance, clumsiness and fine-motor decline. A sudden strabismus or a gallbladder abnormality can also precede clear neurological signs.
Yes. MLD can present with a decline after an infection, peripheral neuropathy on nerve-conduction studies, raised CSF protein and nerve-root enhancement on MRI — a picture that can be mistaken for Guillain-Barré syndrome. In a post-infective regression, MLD should be considered and a brain MRI performed to check for central nervous system involvement.
Early symptoms are subtle and non-specific, so children are often referred to the wrong specialist and the picture is misread as developmental delay, inattention or an orthopaedic problem. Early brain MRI can be normal, particularly before 18–24 months, so a normal scan does not exclude MLD.
Arylsulfatase A enzyme activity and sulfatide levels — including on dried blood spots — give an answer in hours to days, whereas broad genetic panels can take weeks and may miss difficult variants. Biochemical testing is the fastest route to identify affected children, confirmed by genetic testing.
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.