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In this educational webinar, Dr. Martin Magner, a pediatrician and geneticist at Charles University in Prague, presents a detailed overview of Alpha-mannosidosis (AM), focusing on early recognition of its clinical signs and how it overlaps with other lysosomal storage disorders, especially mucopolysaccharidoses (MPS). Emphasizing the importance of timely diagnosis, Dr. Magner provides insights into the natural course of the disease, the variability in presentation, and diagnostic strategies.
Alpha-mannosidosis is an ultra-rare, autosomal recessive disorder caused by mutations in the MAN2B1 gene. This results in deficient activity of the alpha-mannosidase enzyme and subsequent accumulation of oligosaccharides within lysosomes. Though the incidence is estimated at 1 in 500,000 to 1 million live births, Dr. Magner argues that the condition is likely underdiagnosed due to its broad and often subtle presentation.
Clinically, AM is a multisystemic disease, typically presenting in early childhood. Common signs include developmental delay, hearing loss, recurrent infections (often due to underlying immunodeficiency), coarse facial features, skeletal abnormalities, hepatosplenomegaly, and ataxia. Dr. Magner discusses the traditional classification into three phenotypes—mild, moderate, and severe—but explains that a continuous clinical spectrum is a more accurate model.
A key focus is the similarity between AM and neuropathic forms of MPS (particularly MPS I, II, and VI). He highlights overlapping features such as hernias, macrocephaly, respiratory infections, and coarse facial features, but also identifies features more specific to AM: immunodeficiency, psychiatric manifestations (including confusion and hallucinations), and a generally slower disease progression.
The lecture is supplemented with clinical case studies, radiological comparisons, and developmental trajectory charts. Dr. Magner demonstrates how early signs—such as mild dysmorphia or delayed speech—are frequently overlooked, contributing to diagnostic delays of several years. He stresses that early cognitive decline, hearing impairment, and recurrent ENT infections should prompt further investigation for AM.
Diagnostic tools include enzyme assays, urinary oligosaccharide screening, genetic testing, and MRI, which may show white matter changes or cerebral atrophy. Dr. Magner concludes with a call for increased awareness among pediatricians, emphasizing that early diagnosis improves access to enzyme replacement therapy and other interventions. He recommends dry blood spot (DBS) testing as a practical tool when MPS is suspected but initial tests are inconclusive.