Hearing Impairment in Alpha-Mannosidosis: Case Series

Background . Alpha-mannosidosis is a rare hereditary disorder belonging to the group of lysosomal storage diseases, characterized by a wide spectrum of clinical manifestations, including hearing impairment, which is often one of the first symptoms. The mixed nature of hearing loss, along with the polymorphism of the clinical presentation, contributes to diagnostic difficulties. The aim of this study is to analyze case series to raise awareness among physicians about alpha-mannosidosis. Case series : Two case reports of type 2 alpha-mannosidosis in children are presented. In the first case report, a 3-year-5-month-old girl with psychomotor developmental delay and a specific phenotype was diagnosed with bilateral severe hearing loss. An interdisciplinary approach and the vigilance of an audiologist allowed for timely biochemical and genetic diagnostics (a homozygous pathogenic variant c.2248C>T in the MAN2B1 gene was identified) and the initiation of enzyme replacement therapy at the age of 3 years 10 months. In the second case report, diagnosis was delayed in two sisters born from a consanguineous marriage: hearing impairment and speech development delay were identified late, hearing aids were provided with a delay, and low compliance was noted. Large deletions in the MAN2B1 gene were genetically confirmed. The late initiation of treatment and the age of primary hearing aid fitting resulted in a lack of significant positive dynamics in auditory-verbal development. Conclusion. The presented case series highlight the critical importance of early diagnosis of alpha-mannosidosis. “Unexplained” mixed or sensorineural hearing loss, especially when combined with psychomotor developmental delay, dysmorphic facial features, and recurrent otitis media, requires the exclusion of lysosomal storage disorders. Timely interdisciplinary examination, including assessment of lysosomal enzyme activity, enables diagnosis verification and initiation of pathogenetic therapy, thereby improving the disease prognosis.