Clinical Biomarkers in Alpha-Mannosidosis

Alpha-mannosidosis (AMD) is an inherited lysosomal storage disorder caused by mutations in the LAMAN gene, which encodes lysosomal alpha-mannosidase and is characterized by neurodevelopmental delay, mild immune deficiency, facial and skeletal abnormalities, hearing impairment, intellectual disability, muscle weakness and ataxia. Neuromuscular and skeletal deterioration progresses over decades, rendering most patients wheel-chair dependent. No consistently successful treatment is available. To better characterize the biochemical phenotype and natural history of this disorder, patients with AMD were recruited, ranging in age from five to 60 years, mainly in the US and Canada. Participants in the study visited the NIH Clinical Center for 2-3 days during which they underwent clinical and biochemical evaluations to establish reliable clinical benchmarks and to identify cerebrospinal fluid biomarkers that could serve as candidate surrogate markers of treatment effect in future clinical trials.