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A 60-minute educational webinar with Dr Nathalie Guffon (Reference Centre for Inherited Metabolic Diseases, Lyon) and Dr Sonia Ayari (ENT, Lyon) on hearing impairment as an early red flag in the differential diagnosis of alpha-mannosidosis — the ENT manifestations, the hearing loss, and how to distinguish it from other lysosomal storage disorders. For paediatricians, ENT specialists and metabolic teams.
Alpha-mannosidosis is a rare, progressive, multisystemic lysosomal storage disease caused by MAN2B1 mutations and alpha-mannosidase deficiency, presenting with speech delay, recurrent infections, immune dysfunction, cognitive impairment, skeletal abnormalities and psychiatric manifestations. Dr Sonia Ayari details the ENT features that often appear early: recurrent or chronic otitis media, persistent nasal congestion, snoring and rhinopharyngitis, with adenoid hypertrophy — and, crucially, symptoms that resist or recur after adenoidectomy and ventilation tubes. Early-onset (before 12 months) and treatment-resistant ENT symptoms should prompt further investigation. Sensorineural hearing loss is the most common type (found in 75–100% of published patients and up to 93% in one series), is frequently the first clinical sign, and often precedes the diagnosis by years — so hearing testing should be repeated after ventilation tubes to detect it. Dr Nathalie Guffon frames hearing impairment as a red flag: it should prompt suspicion when not isolated but combined with recurrent infection (especially with IgG deficiency), clumsiness and poor coordination, learning difficulties, macrocephaly, coarse facial features or skeletal signs such as genu valgum. Diagnosis rests on urinary oligosaccharides, the alpha-mannosidase enzyme assay and MAN2B1 genetic testing — and including the gene in hearing-loss panels can improve early detection. She distinguishes alpha-mannosidosis from the mucopolysaccharidoses and mucolipidoses and, through two illustrative cases, reinforces multidisciplinary awareness and early referral.
After viewing this webinar, participants will be able to:
Because sensorineural hearing loss is the most common feature (found in 75–100% of published patients) and is frequently the first clinical sign — yet the diagnosis is often delayed by years after it is identified. Recognising hearing impairment, especially when not isolated, is therefore a key route to earlier diagnosis.
Recurrent or chronic otitis media, persistent nasal congestion, snoring and rhinopharyngitis with adenoid hypertrophy — with the important clues being early onset (usually before one year, sometimes before six months), persistence or recurrence despite adenoidectomy and ventilation tubes, and association with other systemic signs. Hearing testing should be repeated after ventilation tubes to detect an associated sensorineural loss.
When it is not isolated but combined with other red flags: recurrent infection (especially with IgG deficiency, or infections beyond the ENT such as pneumonia or arthritis), clumsiness and poor coordination with normal vestibular function, learning difficulties despite hearing aids, macrocephaly, subtle coarse facial features, or skeletal signs such as genu valgum or kyphoscoliosis.
By urinary oligosaccharides (elevated mannose-rich oligosaccharides), the alpha-mannosidase enzyme assay in leukocytes or on a dried blood spot, and MAN2B1 genetic testing — which can be included in hearing-loss panels. It shares features with the mucopolysaccharidoses but is slower, with longer survival, and differs by its immunodeficiency-related infections, psychiatric manifestations and ataxia, while carpal tunnel syndrome and craniocervical instability (typical of MPS) are uncommon.
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.