Diagnosis of alpha-Mannosidosis: Practical approaches to reducing diagnostic delays in this ultra-rare disease.

Autor: Santoro L; Department of Clinical Sciences, Division of Pediatrics, Polytechnic University of Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy. Electronic address: dott.luciasantoro@gmail.com., Cefalo G; Clinical Department of Pediatrics, ASST Santi Paolo e Carlo, San Paolo Hospital, University of Milan, Milan, Italy. Electronic address: graziella.cefalo@asst-santipaolocarlo.it., Canalini F; Chiesi Italia SPA, Parma, Italy. Electronic address: f.canalini@chiesi.com., Rossi S; Chiesi Italia SPA, Parma, Italy. Electronic address: silvia.rossi14576@gmail.com., Scarpa M; Regional Coordinating Center for Rare Diseases, Udine University Hospital, P.le S. Maria della Misericordia 15, Udine 33100, Italy. Electronic address: maurizio.scarpa@asufc.sanita.fvg.it.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2024 May; Vol. 142 (1), pp. 108444. Date of Electronic Publication: 2024 Mar 14.
DOI: 10.1016/j.ymgme.2024.108444
Abstrakt: Alpha-mannosidosis is an ultra-rare lysosomal disease that is caused by variants of the MAN2B1 gene on chromosome 19p13. These variants result in faulty or absent alpha-mannosidase in lysosomes, which leads to intracellular accumulation of mannose-containing oligosaccharides. Diagnosis of alpha-mannosidosis is often delayed, in part because of the rarity of the disease, its gradual onset and heterogeneity of presentation, but also because of the similarity of many signs and symptoms of the disease to those of other lysosomal diseases. Treatment of alpha-mannosidosis was previously limited to hematopoietic stem cell transplantation, but outcomes are variable and not all patients are eligible or have a suitable donor. Recently, an enzyme replacement therapy, recombinant human alpha-mannosidase (velmanase alfa), was approved for the treatment of non-neurological manifestations in adult and pediatric patients with alpha-mannosidosis. Treatment with velmanase alfa reduces serum levels of oligosaccharides, increases levels of immunoglobulin G, and improves patients' functional capacity and quality of life, although it is not effective for the neurologic phenotype because it does not cross the blood-brain barrier. Since the effects of velmanase alfa are more marked in children than adults, early diagnosis to allow early initiation of treatment has become more important. To support this, patient, parent/caregiver, and clinician awareness and education is imperative. A number of approaches can be taken to meet this goal, such as the development of disease registries, validated diagnostic algorithms, and screening tools, improved under-/post-graduate clinician education, easily accessible and reliable information for patients/families (such as that made available on the internet), and the formation of patient advocacy groups. Such approaches may raise awareness of alpha-mannosidosis, reduce the diagnostic delay and thus improve the lives of those affected.
Competing Interests: Declaration of competing interest LS: taught a course on alpha mannosidosis to pediatricians in Jesi (Marche) on behalf of Chiesi Farmaceutici SPA, on 13 April and 8 June 2019, and was involved in a video interview on alpha mannosidosis causes, symptoms, and management (Milan, 20 September 2019), which was broadcasted on the “Discover Alpha Mannosidosis” YouTube channel. GC: participated in advisory boards and received honoraria from Chiesi Farmaceutici SPA. FC: is an employee of Chiesi Italia SPA. SR: was an employee of Chiesi Italia SPA at the time the review was conceptualized and the manuscript written and edited. MS: has received honoraria and travel support from Alexion, United States, BioMarin, Chiesi Farmaceutici SPA, Orchard, Regenxbio, United States, Sanofi, United STates, Takeda, and Ultragenyx, Unites States.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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