A Comprehensive Review of Pathogenesis, Clinical Manifestations, Diagnostic Evaluation and Management of Alpha-Mannosidosis: Rare Genetic Disorder

Abstract

Alpha-mannosidosis is a rare genetic condition where the lysosomal alpha-mannosidase enzyme is deficient as a result of mutations in the MAN2B1 gene. An accumulation of mannose-rich oligosaccharides is the consequence of this shortage in different tissues, causing a wide range of symptoms, including immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It is estimated that one in every million babies born worldwide suffers from this condition. Diagnosis involves measuring acid alpha-mannosidase activity, genetic testing, and assessing increased mannose-rich oligosaccharides in urine. The condition is typically managed through supportive care, with treatments aimed at preventing and alleviating its consequences. Hematopoietic stem cell transplantation (HSCT) may be considered for younger patients, while enzyme replacement therapy (ERT) with Velmanase alfa, approved in the United States, offers a targeted therapy option to restore normal cellular activity. Poor long-term prognosis exists. Neuromuscular and skeletal degeneration progresses slowly over several decades, keeping a lot of patients wheelchair-dependent. Despite its rarity, understanding the clinical types, diagnostic methods, and treatment options, including recent advances like enzyme replacement therapy, is crucial for effective management. There is hope for improving prognosis and quality of life for those with this difficult condition because of ongoing research and medicinal advances.