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A 30-minute educational webinar with Prof. Martin Magner (Charles University, Prague) on spotting the early signs of alpha-mannosidosis, a rare lysosomal storage disease. He sets out how it overlaps with — and differs from — the mucopolysaccharidoses (MPS), and why early recognition matters. For paediatricians and metabolic teams.
Alpha-mannosidosis is an ultra-rare, autosomal recessive lysosomal storage disease caused by variants in the MAN2B1 gene, which encodes alpha-mannosidase; its deficiency leads to storage of oligosaccharides in lysosomes and multisystemic disease. First described by Öckerman in 1967, it has an estimated incidence of 1 in 500,000 to 1 in 1 million, but is likely under-diagnosed. Prof. Martin Magner sets out the main features — hearing loss, skeletal involvement, cognitive impairment, immunodeficiency with recurrent infections, coarse facial features, ataxia and psychiatric symptoms — and explains that the traditional three types are better understood as a continuous spectrum, with most patients in the moderate range. A central theme is the overlap with the neuronopathic mucopolysaccharidoses (particularly MPS I, II and VI): shared features include organomegaly, hernias, developmental delay, coarse facial features, hearing disorder, macrocephaly and recurrent respiratory infections, while immunodeficiency, psychosis, ataxia and a generally slower progression are more specific to alpha-mannosidosis. Using cohort data, case images and developmental charts, Magner shows how mild early signs — subtle dysmorphia, delayed speech, recurrent ENT infections — are frequently overlooked, giving a diagnostic delay of about five years. He stresses that a combination of two or three suggestive symptoms should prompt testing (urinary oligosaccharides, the alpha-mannosidase enzyme assay and MAN2B1 genetic testing), and that a dried-blood-spot test is a practical tool when MPS is suspected but the initial screen is negative.
After viewing this webinar, participants will be able to:
Alpha-mannosidosis is an ultra-rare, autosomal recessive lysosomal storage disease caused by variants in the MAN2B1 gene, which encodes the enzyme alpha-mannosidase. Its deficiency leads to storage of oligosaccharides in lysosomes, producing a progressive, multisystemic disease with hearing loss, cognitive impairment, immunodeficiency, skeletal changes and, later, ataxia and psychiatric symptoms.
They share many features — organomegaly, hernias, developmental delay, coarse facial features, hearing disorder, macrocephaly and recurrent respiratory infections — but immunodeficiency, psychosis, ataxia and a generally slower progression are more specific to alpha-mannosidosis, while carpal tunnel syndrome and craniocervical instability, typical of MPS, are not features of it. Patients with alpha-mannosidosis generally live longer than those with neuronopathic MPS.
Because the early signs are mild and non-specific — subtle facial features, delayed speech, recurrent ENT infections — and are easily attributed to common childhood problems. Although the first symptoms often appear in the first year of life, the diagnostic delay is about five years, so clinicians should look for the combination of signs rather than each in isolation.
Urinary oligosaccharide screening (showing mannose-rich oligosaccharides), the alpha-mannosidase enzyme assay in leukocytes, and MAN2B1 genetic testing. A dried-blood-spot test is a practical option — especially useful when a mucopolysaccharidosis is suspected but the initial MPS screen is negative.
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.