Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency,[5] is a disorder of oligosaccharide metabolism caused by decreased activity of the enzyme beta-mannosidase. This enzyme is coded for by the gene MANBA, located at 4q22-25. Beta-mannosidosis is inherited in an autosomal recessive manner.[5] Affected individuals appear normal at birth, and can have a variable clinical presentation. Infantile onset forms show severe neurodegeneration, while some children have intellectual disability. Hearing loss and angiokeratomas are common features of the disease.[3][2]
The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome.[5] People have been described with a wide spectrum of clinical presentations, from infants and children with intellectual disability to adults who present with isolated skin findings (angiokeratomas).[5]
Most cases are identified in the first year of life with respiratory infections, hearing loss and intellectual disability. Because of its rarity, and non-specific clinical findings, beta-mannosidosis can go undiagnosed until adulthood, where it can present with intellectual disability and behavioral problems, including aggression.[6][1]
Cause
In terms of causation, several mutations in the MANBA gene are the cause of beta-mannosidosis. The cytogenetic location of the gene is 4q24; furthermore, the condition is inherited in an autosomal recessive manner.[7][2]
The pathophysiology of this condition is better comprehended if one first looks at the normal function of beta-mannosidase, such as its function of breaking down disaccharides.[medical citation needed]
Beta-mannosidase function is consistent with it being a lysosomal enzyme catalyzing and thus involved in degradation route for N-linked oligosaccharide moieties (glycoproteins).[8]
Diagnosis
Urine test
A diagnosis of beta-mannosidosis is suspected based on the person's clinical presentation. Urine testing to identify abnormal oligosaccharides is a useful screening test, and enzymatic analysis or molecular testing can be used for confirmation.[3]
^ abcReference, Genetics Home. "beta-mannosidosis". Genetics Home Reference. Retrieved 2017-07-13.
^ abcEnns, Gregory M.; Steiner, Robert D.; Cowan, Tina M. (2009). "Lysosomal Disorders". In Sarafoglou, Kiriakie; Hoffmann, Georg F.; Roth, Karl S. (eds.). Pediatric Endocrinology and Inborn Errors of Metabolism (1st ed.). New York: McGraw-Hill Medical. pp. 721–755. ISBN978-0-07-143915-2.
^Johnson, William (2015). Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth ed.). Academic Press. pp. 369–383. ISBN978-0-12-410529-4.
Further reading
Molho-Pessach, Vered; Bargal, Ruth; Abramowitz, Yigal; Doviner, Victoria; Ingber, Arieh; Raas-Rothschild, Annick; Ne'eman, Zvi; Zeigler, Marsha; Zlotogorski, Abraham (2007). "Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation". Journal of the American Academy of Dermatology. 57 (3): 407–412. doi:10.1016/j.jaad.2007.01.037. ISSN1097-6787. PMID17420068.
