Beta-mannosidosis

Beta-mannosidosis
Beta-mannosidosis
Other names	Beta-mannosidase deficiency, MANSB
	This condition is autosomal recessive in inheritance
Specialty	Medical genetics
Symptoms	Respiratory infections, Hearing loss and Intellectual disability.
Causes	Mutations in the MANBA gene
Diagnostic method	Urine test
Treatment	Based on symptoms

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

Angiokeratoma

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]

Mechanism

Mannose

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]

Differential diagnosis

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

Treatment

There is currently no treatment available; individuals exhibiting muscle weakness or seizures are treated based on symptoms.^[4]

References

^ ^a ^b "Mannosidosis, beta A, lysosomal | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2018-01-02. Retrieved 2017-07-13.
^ ^a ^b ^c Reference, Genetics Home. "beta-mannosidosis". Genetics Home Reference. Retrieved 2017-07-13.
^ ^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.
^ ^a ^b Kelly, Evelyn B. (2013). Encyclopedia of Human Genetics and Disease. ABC-CLIO. p. 514. ISBN 9780313387135. Retrieved 10 December 2017.
^ ^a ^b ^c ^d Online Mendelian Inheritance in Man (OMIM): 248510
^ 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
^ Reference, Genetics Home. "MANBA gene". Genetics Home Reference. Retrieved 2017-10-25.
^ "OMIM Entry - * 609489 - MANNOSIDASE, BETA A, LYSOSOMAL; MANBA". www.omim.org. Retrieved 9 May 2018.
^ 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.

External links

Scholia has a topic profile for Beta-mannosidosis.

[gard-1] "Mannosidosis, beta A, lysosomal | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 2018-01-02. Retrieved 2017-07-13.

[nih1-2] Reference, Genetics Home. "beta-mannosidosis". Genetics Home Reference. Retrieved 2017-07-13.

[pedsendo-3] 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.

[ency-4] Kelly, Evelyn B. (2013). Encyclopedia of Human Genetics and Disease. ABC-CLIO. p. 514. ISBN 9780313387135. Retrieved 10 December 2017.

[omim-5] Online Mendelian Inheritance in Man (OMIM): 248510

[review-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.

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