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| {{Infobox medical condition (new) | | {{Short description|A rare genetic disorder affecting glycoprotein metabolism}} |
| | name = <!--{{PAGENAME}} by default--> | |
| | synonym = Beta-mannosidase deficiency, MANSB
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| | image = Autosomal recessive - en.svg
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| | caption = This condition is autosomal recessive in inheritance
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| | specialty = <!-- from Wikidata, can be overwritten -->
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| | symptoms = Respiratory infections, Hearing loss and Intellectual disability.<ref name=gard/>
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| | causes = Mutations in the MANBA gene<ref name=nih1/>
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| | diagnosis = Urine test<ref name=pedsendo/>
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| | treatment = Based on symptoms<ref name=ency/>
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| '''Beta-mannosidosis''', also called '''lysosomal beta-mannosidase deficiency''',<ref name = omim>{{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 ''[[Beta-mannosidase|MANBA]]'', located at [[chromosome 4 (human)|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>{{cite book |last1=Enns |first1=Gregory M. |last2=Steiner |first2=Robert D. |last3=Cowan |first3=Tina M. |editor1-first=Kiriakie |editor1-last=Sarafoglou |editor2-first=Georg F. |editor2-last=Hoffmann |editor3-first=Karl S. |editor3-last=Roth |others= |title=Pediatric Endocrinology and Inborn Errors of Metabolism |edition=1st |year=2009 |publisher=McGraw-Hill Medical |location=New York |isbn= 978-0-07-143915-2 |pages=721–755 |chapter=Lysosomal Disorders}}</ref><ref name="nih1">{{Cite web|url=https://ghr.nlm.nih.gov/condition/beta-mannosidosis|title=beta-mannosidosis|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2017-07-13}}</ref>
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| ==Symptoms and signs==
| | '''Beta-mannosidosis''' is a rare [[lysosomal storage disorder]] caused by a deficiency of the enzyme beta-mannosidase. This enzyme deficiency leads to the accumulation of mannose-containing [[oligosaccharides]] in the body, resulting in a variety of clinical symptoms. |
| [[File:Angiokreatoma.jpg|thumb|left|140 px|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 />
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| 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>{{Cite journal | last1 = Sedel | first1 = F. | last2 = Baumann | first2 = N. | last3 = Turpin | first3 = J. -C. | last4 = Lyon-Caen | first4 = O. | last5 = Saudubray | first5 = J. -M. | last6 = Cohen | first6 = D. | doi = 10.1007/s10545-007-0661-4 | title = Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults | journal = Journal of Inherited Metabolic Disease | volume = 30 | issue = 5 | pages = 631–641 | year = 2007 | pmid = 17694356 | pmc = }}subscription required</ref><ref name="gard">{{Cite web|url=https://rarediseases.info.nih.gov/diseases/869/index|title=Mannosidosis, beta A, lysosomal {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|language=en|access-date=2017-07-13}}</ref>
| | ==Pathophysiology== |
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| | Beta-mannosidosis is an [[autosomal recessive]] disorder, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. The condition is caused by mutations in the MANBA gene, which encodes the enzyme beta-mannosidase. This enzyme is responsible for breaking down complex sugars in the [[lysosome]], a cellular organelle involved in the degradation of macromolecules. |
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| ==Cause==
| | In individuals with beta-mannosidosis, the lack of functional beta-mannosidase leads to the accumulation of mannose-rich oligosaccharides in various tissues, including the [[central nervous system]], [[kidneys]], and [[liver]]. This accumulation disrupts normal cellular function and leads to the clinical manifestations of the disease. |
| In terms of causation several [[mutations]] in the [[Beta-mannosidase|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>{{Cite web|url=https://ghr.nlm.nih.gov/gene/MANBA#location|title=MANBA gene|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2017-10-25}}</ref><ref name=nih1/> | |
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| ==Mechanism== | | ==Clinical Features== |
| | The symptoms of beta-mannosidosis can vary widely among affected individuals, but common features include: |
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| [[File:Mannose structure.svg|thumb|170 px|[[Mannose]] ]] | | * [[Intellectual disability]] |
| 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 [[disaccharide]]s{{medical citation needed|date=December 2017}}
| | * [[Hearing loss]] |
| | * [[Speech delay]] |
| | * [[Motor dysfunction]] |
| | * [[Recurrent infections]] |
| | * [[Skeletal abnormalities]] |
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| 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>{{cite web|title=OMIM Entry - * 609489 - MANNOSIDASE, BETA A, LYSOSOMAL; MANBA|url=https://www.omim.org/entry/609489|website=www.omim.org|accessdate=9 May 2018|language=en-us}}</ref>
| | The severity of symptoms can range from mild to severe, and the age of onset can vary from infancy to adulthood. |
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| ==Diagnosis== | | ==Diagnosis== |
| [[File:Weewee.JPG|thumb|30 px|left|Urine test]]
| | Diagnosis of beta-mannosidosis is typically based on clinical evaluation, biochemical testing, and genetic analysis. Biochemical testing involves measuring the activity of beta-mannosidase in leukocytes or fibroblasts. Genetic testing can confirm the diagnosis by identifying mutations in the MANBA gene. |
| 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 />
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| ===Differential diagnosis===
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| Diagnostic techniques for this condition can be done to offer a DDx, via [[lectin]] [[histochemistry]] to distinguish between α-mannosidosis and beta-mannosidosis.<ref>{{cite book|last1=Johnson|first1=William|title=Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Fifth Edition)|date=2015|publisher=Academic Press|isbn=978-0-12-410529-4|pages=369–383|url=}}</ref>
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| ==Treatment== | | ==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">{{cite book|last1=Kelly|first1=Evelyn B.|title=Encyclopedia of Human Genetics and Disease|date=2013|publisher=ABC-CLIO|isbn=9780313387135|page=514|url=https://books.google.com/?id=gqMYt17klVIC&pg=PA514&dq=beta-mannosidosis+treatment#v=onepage&q=beta-mannosidosis%20treatment&f=false|accessdate=10 December 2017|language=en}}</ref>
| | Currently, there is no cure for beta-mannosidosis, and treatment is primarily supportive and symptomatic. Management may include: |
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| ==See also==
| | * [[Physical therapy]] and [[occupational therapy]] to improve motor skills |
| *[[Beta-mannosidase]] | | * [[Speech therapy]] to address communication difficulties |
| *[[Alpha-mannosidosis]] | | * [[Hearing aids]] or other interventions for hearing loss |
| | * Regular monitoring and treatment of infections |
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| ==References==
| | Research into potential therapies, such as enzyme replacement therapy and gene therapy, is ongoing. |
| {{Reflist|32em}}
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| ==Further reading== | | ==Prognosis== |
| *{{cite journal|last1=Molho-Pessach|first1=Vered|last2=Bargal|first2=Ruth|last3=Abramowitz|first3=Yigal|last4=Doviner|first4=Victoria|last5=Ingber|first5=Arieh|last6=Raas-Rothschild|first6=Annick|last7=Ne'eman|first7=Zvi|last8=Zeigler|first8=Marsha|last9=Zlotogorski|first9=Abraham|title=Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation|journal=Journal of the American Academy of Dermatology|volume=57|issue=3|pages=407–412|doi=10.1016/j.jaad.2007.01.037|issn=1097-6787|pmid=17420068|year=2007}}
| | The prognosis for individuals with beta-mannosidosis varies depending on the severity of the condition. Some individuals may lead relatively normal lives with appropriate supportive care, while others may experience significant disability. |
| *{{cite journal|last1=Huynh|first1=T|last2=Khan|first2=JM|last3=Ranganathan|first3=S|title=A comparative structural bioinformatics analysis of inherited mutations in β-D-Mannosidase across multiple species reveals a genotype-phenotype correlation.|journal=BMC Genomics|date=30 November 2011|volume=12 Suppl 3|pages=S22|doi=10.1186/1471-2164-12-S3-S22|pmid=22369051|issn=1471-2164|pmc=3333182}}
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| ==External links== | | ==Related pages== |
| {{Medical resources
| | * [[Lysosomal storage disorder]] |
| | DiseasesDB = 34529
| | * [[Autosomal recessive disorder]] |
| | ICD10 = E77.1
| | * [[Enzyme replacement therapy]] |
| | ICD9 =
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| | ICDO =
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| | OMIM = 248510
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| | MedlinePlus =
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| | eMedicineSubj =
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| | eMedicineTopic =
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| | MeshID = D044905
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| | Orphanet = 118
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| }}
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| {{Glycoproteinoses}}
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| {{Medicine}}
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| [[Category:Glycoprotein metabolism disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Rare diseases]] | | [[Category:Lysosomal storage diseases]] |
| [[Category:Autosomal recessive disorders]]
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| {{dictionary-stub1}}
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A rare genetic disorder affecting glycoprotein metabolism
Beta-mannosidosis is a rare lysosomal storage disorder caused by a deficiency of the enzyme beta-mannosidase. This enzyme deficiency leads to the accumulation of mannose-containing oligosaccharides in the body, resulting in a variety of clinical symptoms.
Pathophysiology
Beta-mannosidosis is an autosomal recessive disorder, meaning that an individual must inherit two copies of the defective gene, one from each parent, to manifest the disease. The condition is caused by mutations in the MANBA gene, which encodes the enzyme beta-mannosidase. This enzyme is responsible for breaking down complex sugars in the lysosome, a cellular organelle involved in the degradation of macromolecules.
In individuals with beta-mannosidosis, the lack of functional beta-mannosidase leads to the accumulation of mannose-rich oligosaccharides in various tissues, including the central nervous system, kidneys, and liver. This accumulation disrupts normal cellular function and leads to the clinical manifestations of the disease.
Clinical Features
The symptoms of beta-mannosidosis can vary widely among affected individuals, but common features include:
The severity of symptoms can range from mild to severe, and the age of onset can vary from infancy to adulthood.
Diagnosis
Diagnosis of beta-mannosidosis is typically based on clinical evaluation, biochemical testing, and genetic analysis. Biochemical testing involves measuring the activity of beta-mannosidase in leukocytes or fibroblasts. Genetic testing can confirm the diagnosis by identifying mutations in the MANBA gene.
Treatment
Currently, there is no cure for beta-mannosidosis, and treatment is primarily supportive and symptomatic. Management may include:
Research into potential therapies, such as enzyme replacement therapy and gene therapy, is ongoing.
Prognosis
The prognosis for individuals with beta-mannosidosis varies depending on the severity of the condition. Some individuals may lead relatively normal lives with appropriate supportive care, while others may experience significant disability.
Related pages
