Beta-mannosidosis

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Beta-mannosidosis
Other namesBeta-mannosidase deficiency, MANSB
Autosomal recessive - en.svg
This condition is autosomal recessive in inheritance
SpecialtyMedical genetics Edit this on Wikidata
SymptomsRespiratory infections, Hearing loss and Intellectual disability.[1]
CausesMutations in the MANBA gene[2]
Diagnostic methodUrine test[3]
TreatmentBased on symptoms[4]

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]

Symptoms and signs

Angiokreatoma

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 is 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]

Mechanism

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 persons 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]

Differential diagnosis

Diagnostic techniques for this condition can be done to offer a DDx, via lectin histochemistry to distinguish between α-mannosidosis and beta-mannosidosis.[9]

Treatment

In terms of beta-mannosidosis treatment there is none currently, individuals that exhibit muscle weakness or seizures are treated based on the symptoms (since there's no cure)[4]

See also

References

  1. ^ a b "Mannosidosis, beta A, lysosomal | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-07-13.
  2. ^ a b c Reference, Genetics Home. "beta-mannosidosis". Genetics Home Reference. Retrieved 2017-07-13.
  3. ^ a b c Enns, 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. ISBN 978-0-07-143915-2.
  4. ^ a b Kelly, Evelyn B. (2013). Encyclopedia of Human Genetics and Disease. ABC-CLIO. p. 514. ISBN 9780313387135. Retrieved 10 December 2017.
  5. ^ a b c d Online Mendelian Inheritance in Man (OMIM): 248510
  6. ^ Sedel, F.; Baumann, N.; Turpin, J. -C.; Lyon-Caen, O.; Saudubray, J. -M.; Cohen, D. (2007). "Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults". Journal of Inherited Metabolic Disease. 30 (5): 631–641. doi:10.1007/s10545-007-0661-4. PMID 17694356. S2CID 8419283.subscription required
  7. ^ Reference, Genetics Home. "MANBA gene". Genetics Home Reference. Retrieved 2017-10-25.
  8. ^ "OMIM Entry - * 609489 - MANNOSIDASE, BETA A, LYSOSOMAL; MANBA". www.omim.org. Retrieved 9 May 2018.
  9. ^ Johnson, William (2015). Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth ed.). Academic Press. pp. 369–383. ISBN 978-0-12-410529-4.

Further reading

External links

Classification
External resources