Lysosomal alpha-mannosidase and alpha-mannosidosis
Abstract
Lysosomal alpha-mannosidase with acidic pH optimum is ubiquitous in human tissues where is expressed in two major forms, A and B that are the product of a single gene located on chromosome 19. Mutations in the gene encoding for alpha-mannosidase cause alpha- mannosidosis, an autosomal recessive disease, resulting in the accumulation of unprocessed mannose containing oligosaccharide material. This rare disease has an estimated incidence of 1/500.0.00 live births and clinically is divided into three subgroups. Today the most promising therapy for this disease is the enzyme replacement therapy. To develop this strategy a mouse model for alpha-mannosidosis has been generated and a recombinant human alpha-mannosidase has been produced from Chinese-hamster ovary cells. Interestingly it has been shown that the recombinant enzyme, used in high dose, can cross the blood brain barrier. This recombinant enzyme has been tested in the first randomized study investigating the efficacy of enzyme replacement therapy in patients with alpha-mannosidosis. This review contains the scientific progresses on lysosomal alpha-mannosidase from the cloning to the beginning of the therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
α-mannosidases are a class of ubiquitous enzymes responsible for the hydrolysis of single mannose residues and mainly known for their role in N-linked carbohydrate catabolism during glycoprotein turnover.
“α-mannosidases are a class of ubiquitous enzymes responsible for the hydrolysis of single mannose residues and mainly known for their role in N-linked carbohydrate catabolism during glycoprotein turnover (65).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [65]
Cited by
Sorted by citations
Su, A. C. Y., Ding, X. Q., Lau, H. C.-H., Kang, X., Li, Q., Wang, X., Liu, Y., Jiang, L., Lu, Y., Liu, W., et al. (2024) · Gut · doi:10.1136/gutjnl-2023-330835 · Cited by 73 · see citing works
“23 26 To ascertain the role of bacterial α MAN, we constructed a strain of E. coli that expressed the sequence of α MAN in HkyuLL 10 .”
MethodAndreatta, G., Broyart, C., Borghgraef, C., Vadiwala, K., Kozin, V., Polo, A., Bileck, A., Beets, I., Schoofs, L., Gerner, C., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910262116 · Cited by 61 · see citing works
“α-mannosidases are a class of ubiquitous enzymes responsible for the hydrolysis of single mannose residues and mainly known for their role in N-linked carbohydrate catabolism during glycoprotein turnover (65).”
Glycosidase-targeting small molecules for biological and therapeutic applications
Kim, Y., Li, H., Choi, J., Boo, J., Jo, H., Hyun, J. Y., & Shin, I. (2023) · Chemical Society Reviews · doi:10.1039/d3cs00032j · Cited by 60 · see citing works
Venomics of the ectoparasitoid wasp Bracon nigricans
Becchimanzi, A., Avolio, M., Bostan, H., et al. (2020) · BMC Genomics · doi:10.1186/s12864-019-6396-4 · Cited by 39 · see citing works
The Developmental Transcriptome of Aedes albopictus , a Major Worldwide Human Disease Vector
Gamez, S., Antoshechkin, I. A., Méndez‐Sánchez, S. C., & Akbari, O. S. (2020) · G3 Genes Genomes Genetics · doi:10.1534/g3.119.401006 · Cited by 42 · see citing works
Enzyme therapy: a forerunner in catalyzing a healthy society?
Datta, S., Rajnish, K. N., Doss, C. G. P., Samuel, S. M., Ethiraj, S., & Zayed, H. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2020.1787980 · Cited by 38 · see citing works
Enzyme Replacement Therapy for Genetic Disorders Associated with Enzyme Deficiency
Marchetti, M., Faggiano, S., & Mozzarelli, A. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210526144654 · Cited by 36 · see citing works
Pharmacological Chaperones for the Treatment of α-Mannosidosis
Rísquez‐Cuadro, R., Matsumoto, R., Ortega‐Caballero, F., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00153 · Cited by 34 · see citing works
Lee, Z. Y., Loo, J. S. E., Wibowo, A., Mohammat, M. F., & Foo, J. B. (2021) · Carbohydrate Research · doi:10.1016/j.carres.2021.108395 · Cited by 24 · see citing works
Silveira, C. R. F., Cipelli, M., Manzine, C., Rabelo‐Santos, S. H., Zeferino, L. C., Rodríguez, G. R., de Assis, J. B., Hebster, S., Bernadinelli, I., Laginha, F. M., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213184 · Cited by 24 · see citing works
Analysis of the Differentially Expressed Proteins in Donkey Milk in Different Lactation Stages
Zhou, M., Huang, F., Du, X., et al. (2023) · Foods · doi:10.3390/foods12244466 · Cited by 18 · see citing works
“It was reported that collagen can inhibit the production of melanin, maintain the moisture content of the stratum corneum and the integrity of the fiber structure, and have whitening, moisturizing, and wrinkle-removing effects on the skin [55].”
BackgroundGlycoside hydrolases from (hyper)thermophilic archaea: structure, function, and applications
Iacono, R., Lise, F. D., Moracci, M., Cobucci‐Ponzano, B., & Strazzulli, A. (2023) · Essays in Biochemistry · doi:10.1042/ebc20220196 · Cited by 11 · see citing works
Morales‐Quintana, L., & Méndez-Yáñez, Á. (2023) · Plant Molecular Biology · doi:10.1007/s11103-023-01356-2 · Cited by 9 · see citing works
Paege, N., Feustel, S., & Marx‐Stoelting, P. (2024) · Environmental Health · doi:10.1186/s12940-024-01092-0 · Cited by 8 · see citing works
Burlina, A. P., Manara, R., & Gueraldi, D. (2024) · Handbook of clinical neurology · doi:10.1016/b978-0-323-99209-1.00008-9 · Cited by 8 · see citing works
Mkaouar, R., Riahi, Z., Charfeddine, C., Chelly, I., Boudabbous, H., Dallali, H., Bonnet, C., Hechmi, M., Bekri, S., Zitouna, N., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0258202 · Cited by 7 · see citing works
The Application of HPLC-FLD and NMR in the Monitoring of Therapy Efficacy in Alpha-Mannosidosis
Krchňák, M., Kodríková, R., Matulová, M., et al. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2802039 · Cited by 5 · see citing works
“Alpha-mannosidosis (AM) is an ultra-rare, autosomal recessive lysosomal storage disorder (LSD) [1] with an estimated prevalence between 1:500,000 and 1:1,000,000 [2].”
BackgroundAntanasković, A., Stević, I., Gojak, R., Lakić, D., & Јаnkovic, S. (2023) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2023.2271574 · Cited by 4 · see citing works
“It is caused by decreased activity of lysosomal alpha-mannosidase, which leads to the accumulation of mannose-containing oligosaccharides in tissues [2,3].”
BackgroundDrogalin, A., Monteiro, L. S., Alves, M. J., & Castro, T. G. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2209184 · Cited by 2 · see citing works
“Considering the fact that GMII and LMan perform their functions at different pHs within the cell (GMII, pH 6.6; LMan, pH 4.5) (Ashida et al., 2007; Deschamps et al., 2020; Paciotti et al., 2017), the operating pH cannot be an unimportant subject.”
BackgroundInfluentialNew insights on resveratrol supported by magnesium dihydroxide (Revifast®)
Spogli, R., Biagini, A., Presciutti, F., et al. (2024) · Italian Journal of Food Science · doi:10.15586/ijfs.v36i1.2481 · Cited by 2 · see citing works
Alpha-mannosidosis in a family: natural history with an uncommon retinal dystrophy
Sandal, S., Razdan, T. B., Verma, J., et al. (2020) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000361 · Cited by 1 · see citing works
“This autosomal recessive disorder, due to biallelic variations in the MAN2B1 gene results in deficiency of the enzyme, acid alpha-mannosidase that is involved in the degradation of N-linked oligosaccharides (Paciotti et al., 2017).”
BackgroundAlfa-mannosidosis: Frequent Symptoms in Rare Patient
Vashakmadze, N. D., Zhurkova, N. V., Mikhaylova, L. K., et al. (2023) · Вопросы современной педиатрии · doi:10.15690/vsp.v21i6s.2498 · Cited by 1 · see citing works
Audiological and radiological study of eight polish patients with alpha-mannosidosis
Iwanicka‐Pronicka, K., Guzek, A., Sarnecki, J., et al. (2023) · International Journal of Pediatric Otorhinolaryngology · doi:10.1016/j.ijporl.2023.111556 · Cited by 1 · see citing works
Biochemical Characteristics of Point Mutated Goat Lysosome Α- MannosidasePreprint
Wang, Y., Zhang, J., Xiong, H., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1207865/v1
The Role of Computation Deciphering the Mechanism of N-Glycan Processing α-Mannosidases
Gil, S. A. (2022) · Open Access Journal of Biomedical Science · doi:10.38125/oajbs.000401
“In medicine, a deficiency or malfunction of lysosomal α-mannosidase causes alphamannosidosis, a lysosomal storage disorder described in humans, cattle, cats and guinea pigs [1].”
BackgroundBiochemical characteristics of point mutated Capra hircus lysosome α-mannosidase
Wang, Y., Zhang, J., Jun-Yang, T. E. N. G., et al. (2023) · Journal of Veterinary Medical Science · doi:10.1292/jvms.22-0222
“In mammals, LAM activity is associated with oligosaccharide catabolism [4, 26], exhibits a high affinity for SW [17, 28], is sensitive to the inhibition of SW [7].”
BackgroundMethodResultAlanzi, T. S. A., Mohammed, S., Alhashem, A. M., et al. (2024) · Cureus · doi:10.7759/cureus.58922
“Thus, deficient lysosomal alpha-d-mannosidase activity can result in a lysosomal storage disorder (LSD), alpha-mannosidosis, characterized by progressive impairments in motor and neurological functions, skeletal deformities, and immunodeficiency [2,3].”
BackgroundRetrospective Study of Clinical and Genetic Profiles of Alpha‐Mannosidosis Patients From the UAE
Saad, A. K., Al‐Hammadi, T., Al‐Ameri, S., et al. (2025) · JIMD Reports · doi:10.1002/jmd2.70001
Mohanty, A. K., Deshpande, D., Shah, D., Nina, P. B., & Karmodiya, K. (2025) · BMC Genomics · doi:10.1186/s12864-025-11530-z
“The two classes of alpha man-nosidases—GH47 (in golgi) and GH38 (Lysosomal) are involved in N-glycans catabolism, and are ubiquitously present from microbes to humans [43–45].”
Abdelaziz, M. M., Groer, C. E., Weiner, J. D., et al. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.107844
Hearing Impairment in Alpha-Mannosidosis: Case Series
Goleva, M. A., Mefodovskaya, E. K., Снегова, Е. В., et al. (2026) · Педиатрическая фармакология · doi:10.15690/pf.v23i1.3008
- Authors
- Beccari, T.
- Affiliations
- University of Perugia (IT)
- Corresponding author
- Beccari, Tommaso
- ORCID
- Beccari, Tommaso
- Venue
- Frontiers in bioscience
- Publisher
- IMR Press
- Published
- 2017
- Volume
- 22
- Issue
- 1
- Pages
- 157-167
- ISSN
- 1093-4715 (ISSN-L)
- 1093-9946
- DOI
- 10.2741/4478
- OpenAlex
- W2548858977
- Cited by
- 32
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 4
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in bioscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondazione Cassa di Risparmio di Città di Castello
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- lysosomal alpha-mannosidase, alpha-mannosidosis, lysosomal storage disease, genetic mutations, autosomal recessive inheritance, oligosaccharide accumulation, enzyme replacement therapy, recombinant enzyme, blood-brain barrier, mouse model, gene cloning, CHO cells
- MeSH terms
- Animals, Disease Models, Animal, Humans, Lysosomes, alpha-Mannosidosis, Mutation, Recombinant Proteins, alpha-Mannosidase, Enzyme Replacement Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
