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A 30-minute educational webinar with Dr Florian Lagler (Paracelsus Medical University, Salzburg) on what happens after a diagnosis of alpha-mannosidosis — early treatment, the two disease-modifying therapies, and multidisciplinary care from childhood through transition to adult services. For paediatricians and metabolic teams.
Alpha-mannosidosis is a rare, autosomal recessive lysosomal storage disease (about 1 in 500,000) caused by alpha-mannosidase deficiency, with mild-to-moderate intellectual disability and psychiatric symptoms, coarse facial features, immunodeficiency, skeletal abnormalities, hepatosplenomegaly, CNS involvement and progressive hearing loss. Onset is usually in the first years of life, but diagnosis is often delayed by around five years. Dr Florian Lagler explains that the three clinical types are really a spectrum, and that once suspected, the diagnosis is straightforward — alpha-mannosidase enzyme activity in leukocytes, MAN2B1 sequencing, and urinary oligosaccharides as a screen. The session focuses on the two disease-modifying therapies: haematopoietic stem-cell transplantation (HSCT), which can address central nervous system disease if performed early (in a retrospective study of 17 patients, all made developmental progress and the 5.5-year survival was 88%), and enzyme replacement therapy with velmanase alfa, which reduces somatic disease and biomarkers but does not cross the blood–brain barrier, with clearer benefit shown in younger children. Because irreversible complications cannot be undone, early diagnosis and early treatment are decisive. Dr Lagler presents a case combining early enzyme replacement therapy as a bridge to HSCT — a strategy borrowed from MPS management — and emphasises multidisciplinary care, structured transition to adult services, newborn screening, awareness-raising and symptom-checker tools to shorten the diagnostic delay.
After viewing this webinar, participants will be able to:
Two disease-modifying therapies: haematopoietic stem-cell transplantation (HSCT), which can address central nervous system disease when performed early in life, and enzyme replacement therapy with velmanase alfa, which reduces somatic disease and biomarkers but does not cross the blood–brain barrier. Supportive, symptom-based care remains important for all patients.
Because both HSCT and enzyme replacement therapy work best before complications become established — already-manifest disease is largely irreversible. HSCT in particular gives a superior outcome the earlier it is performed, so identifying and treating patients early is decisive for the result.
Yes — a strategy borrowed from mucopolysaccharidosis management is to start enzyme replacement therapy early as a bridge to HSCT, so the patient is treated while awaiting an HLA-matched transplant. A case in the webinar started enzyme replacement therapy shortly after diagnosis and continued it until HSCT, with a very good response.
Through greater awareness so that a suspicion of a rare disease prompts early referral to a specialist centre (the diagnostic gap at least doubles once workup drifts across non-expert settings), through newborn screening as it develops, and through symptom-checker tools that point clinicians towards the right group of diseases.
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.