1 - Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
2 - Inherited Metabolic Disease Reference Center, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
3 - Neurology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
4 - Inherited Metabolic Disease Reference Center,, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
5 - Inherited Metabolic Disease Reference Center, Centro Hospitalar e Universitário Lisboa Norte, Lisboa, Portugal.
6 - Biochemical Genetics Unit, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal.
- Poster no Congresso da Society For The Study Of Inborn Errors Of Metabolism (Jerusalem, 29 de agosto a 1 de setembro de 2023)
Introduction: Alpha-mannosidosis (AM) is an ultra-rare lysosomal storage disease caused by deficiency of alpha-D-mannosidase due to MAN2B1 mutations. Developments in its treatment, with available enzyme replacement therapy (ERT) velmanase alpha and bone marrow transplantation (BMT), highlight the need of an early diagnosis and systematic characterization of this group of patients. Our aim was to characterize the AM patients currently followed in Portuguese reference centers.
Methods: This is a cross-sectional national multicenter study including patients diagnosed with AM in Portugal. All national reference centers were contacted. Data regarding demographics, disease onset, current symptoms, diagnosis and treatment was collected.
Results: We included 9 patients (6 males) with medians for current age of 25 years old (IQR 19-34), age of symptom onset of 2 years old (IQR 1-4) and time until diagnosis of 7 years (IQR 6-27). Clinically, 6 patients had a type 2 phenotype and 3 a type 1. All patients had typical facial features, developmental delay/intellectual disability and sensorineural deafness. Most frequently associated findings were skeletal abnormalities in 7 patients, pyramidal signs in 7, ataxia in 6 and recurrent otitis in 6. Despite their frequency, symptom severity was highly variable. Seven patients were ambulatory and 2 used wheelchair. Diagnosis was done with genetic testing in all patients, leukocyte α-mannosidase activity in 8 patients and urinary oligosaccharides in 7. Four patients are currently treated with ERT and in 1 BMT was performed in the first year of life, with clinical stabilization.
Conclusions: Although alpha-mannosidosis presents a continuum of severity, the core features of facial dysmorphism, deafness and a variable degree of skeletal involvement, recurrent infections and developmental delay are typical. Diagnostic delay was significant and early treatment led to a better outcome, highlighting the need of an early diagnosis and management.
Palavras Chave: alpha-mannosidosis, enzyme replacement therapy , lysosomal storage disease MAN2B1