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Clinical profiles of 134 patients with alpha-mannosidosis from the velmanase alfa clinical program and SPARKLE registry 

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical- Pediatric
  • Secondary Categories:
    • Clinical- Pediatric
Introduction:
Alpha-mannosidosis (AM) is an ultrarare lysosomal disease and its natural history remains poorly understood. First symptoms of AM can manifest between birth and adolescence. The heterogeneous presentation of AM often leads to delayed or missed diagnosis.

Methods:
To better define AM disease presentation, we analyzed medical history data in velmanase alfa-treated patients, before start of treatment, and untreated patients from an integrated dataset of the velmanase alfa clinical development program and the SPARKLE registry (EUPAS29038). Here, we present age-stratified disease characteristics of 134 patients, one of the largest cohorts of patients with AM to be reported.

Results:
Patients were categorized by age at baseline: <6 years (y), n=25; ≥6–<12y, n=29; ≥12–<18y, n=24; ≥18–<35y, n=44; ≥35y, n=12. Eleven affected system organ classes were reported in ≥20% patients, with “infections and infestations” being highest (63%, 84/134). Hearing loss was most common in age groups ≥6y (42%–73%, n=70). In patients <6y, ear infections (48%, 12/25) were highest, followed by hearing loss (40%, 10/25) and upper and lower respiratory infections (each 28%, 7/25). In patients ≥35y, osteoarthropathies (42%, 5/12), and upper (33%, 4/12) and lower (25%, 3/12) respiratory infections were common. In patients ≥6–<12y, speech/language abnormalities (38%, 11/29), and coordination/balance disturbances (28%, 8/29) were frequent, with an increasing proportion of patients experiencing coordination/balance disturbances from 12 to 35y (≥12–<18y: 38%, 9/24; ≥18–<35y: 43%, 19/44). Spine/neck deformities were frequent across most age groups: <6y (24%, 6/25), ≥6–<12y (21%, 6/29), ≥12–<18y (29%, 7/24) and ≥18–<35y (43%, 19/44). Analysis of patient genetic data will be presented.

 

Conclusion:
Respiratory infections, speech/language abnormalities, and musculoskeletal disorders were common across all ages, confirming reported literature. New insights were gained at which ages certain manifestations may occur (e.g., spine/neck deformities in young children [<10y]). Physician awareness of age-specific AM presentations may aid in earlier diagnosis and specific interventions.

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