Beta-mannosidosis

Synonyms	N/A
Pronounce
Field	N/A
Symptoms	Respiratory infections, Hearing loss and Intellectual disability.<ref name=gard/>
Complications
Onset
Duration
Types
Causes	Mutations in the MANBA gene<ref name=nih1/>
Risks
Diagnosis	Urine test<ref name=pedsendo/>
Differential diagnosis
Prevention
Treatment	Based on symptoms<ref name=ency/>
Medication
Prognosis
Frequency
Deaths

Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency,<ref name = omim>Online Mendelian Inheritance in Man (OMIM) 248510 </ref> 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.<ref name=omim /> 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.<ref name=pedsendo>,

 Pediatric Endocrinology and Inborn Errors of Metabolism, 
 1st edition, 
 New York:McGraw-Hill Medical, 
 2009, 
  
  
 ISBN 978-0-07-143915-2, 
  
  
  
 Pages: 721–755,</ref><ref name="nih1">

Reference, Genetics Home. beta-mannosidosis(link). Genetics Home Reference.

Accessed 2017-07-13.

</ref>

Symptoms and signs

File:Angiokreatoma.jpg

Angiokreatoma

The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome.<ref name=omim /> 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).<ref name = omim />

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.<ref name=review>,

 Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults, 
 Journal of Inherited Metabolic Disease, 
 2007,
 Vol. 30(Issue: 5),
 pp. 631–641,
 DOI: 10.1007/s10545-007-0661-4,
 PMID: 17694356,subscription required</ref><ref name="gard">

Mannosidosis, beta A, lysosomal | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program(link). rarediseases.info.nih.gov.

Accessed 2017-07-13.

</ref>

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<ref> Reference, Genetics Home. MANBA gene(link). Genetics Home Reference.

Accessed 2017-10-25.

</ref><ref name=nih1/>

Mechanism

File:Mannose structure.svg

Mannose

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

Beta-mannosidase function is consistent with, it being a lysosomal enzyme catalyzing and thus involved in degradation route for N-linked oligosaccharide moieties(glycoproteins)<ref>

OMIM Entry - * 609489 - MANNOSIDASE, BETA A, LYSOSOMAL; MANBA(link). www.omim.org.

</ref>

Diagnosis

File:Weewee.JPG

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.<ref name=pedsendo />

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.<ref>,

 Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition), 
  
 Academic Press, 
  
  
  
 ISBN 978-0-12-410529-4, 
  
  
  
 Pages: 369–383,</ref>

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)<ref name="ency">,

 Encyclopedia of Human Genetics and Disease. online version, 
  
 ABC-CLIO, 
  
  
  
 ISBN 9780313387135,</ref>

See also

• Beta-mannosidase
• Alpha-mannosidosis

Further reading

• ,

 Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation, 
 Journal of the American Academy of Dermatology, 
 2007,
 Vol. 57(Issue: 3),
 pp. 407–412,
 DOI: 10.1016/j.jaad.2007.01.037,
 PMID: 17420068,

• ,

 A comparative structural bioinformatics analysis of inherited mutations in β-D-Mannosidase across multiple species reveals a genotype-phenotype correlation., 
 BMC Genomics, 
 
 Vol. 12 Suppl 3,
 pp. S22,
 DOI: 10.1186/1471-2164-12-S3-S22,
 PMID: 22369051,
 PMC: 3333182,

External links

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