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This webinar, co-hosted by Dr. Nathalie Guffon and Dr. Sonia Ayari, explores the role of hearing impairment as an early and critical indicator in the differential diagnosis of alpha-mannosidosis (AM). The session offers detailed insights into ENT manifestations, the diagnostic pathway, and distinguishing features of AM compared to other lysosomal storage disorders.
Dr. Guffon begins with an overview of alpha-mannosidosis, a rare, progressive, multisystemic disorder caused by mutations in the MAN2B1 gene. The disease leads to deficient alpha-mannosidase enzyme activity, resulting in the accumulation of mannose-rich oligosaccharides and cellular dysfunction. With an estimated prevalence of 1 in 500,000 live births—though possibly higher due to underdiagnosis—AM presents with variable symptoms including speech delay, recurrent infections, immune dysfunction, cognitive impairment, skeletal abnormalities, and psychiatric manifestations.
Dr. Ayari focuses on the ENT features that often manifest early in AM. These include chronic or recurrent otitis media, persistent nasal congestion, snoring, and rhinopharyngitis. Notably, many children require adenoidectomy and ventilation tube placement, but symptoms often persist or recur post-surgery. She emphasizes that early-onset and treatment-resistant ENT symptoms—particularly before 12 months of age—should prompt further investigation.
A significant portion of the session is dedicated to hearing loss. Sensorineural hearing impairment is the most common type observed in AM patients, followed by mixed hearing loss. This is often accompanied by delayed language development. Studies presented in the webinar indicate hearing loss in up to 93% of patients, and it is frequently the first reported clinical sign. However, diagnosis of AM is often delayed by several years, even after hearing impairment is identified.
Dr. Ayari and Dr. Guffon highlight red flags for referral to metabolic specialists: hearing loss combined with macrocephaly, poor motor coordination, speech delay, coarse facial features, skeletal anomalies (e.g., genu valgum), or recurrent infections, especially if IgG deficiency is present. These overlapping signs, when considered collectively, can significantly raise clinical suspicion for AM.
Diagnostic workup should include urinary oligosaccharides, enzyme activity assays, and genetic testing for MAN2B1 mutations. Including the gene in hearing loss panels may improve early detection.
The session concludes with case studies and a discussion reinforcing the value of multidisciplinary awareness and early referral for timely diagnosis and intervention.