Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2020 Jul 10;55(1):15-21.
doi: 10.1002/jmd2.12144. eCollection 2020 Sep.

Early biochemical effects of velmanase alfa in a 7-month-old infant with alpha-mannosidosis

Lucia Santoro  1 , Lucia Zampini  1 , Lucia Padella  1 , Chiara Monachesi  1 , Stefania Zampieri  2 , Andrea Dardis  2 , Rosanna Cordiali  1 , Tiziana Galeazzi  1 , Carlo Catassi  1
Affiliations
Case Reports

Early biochemical effects of velmanase alfa in a 7-month-old infant with alpha-mannosidosis

Lucia Santoro et al. JIMD Rep. .

Abstract

Alpha mannosidosis is an ultrarare pathology with variable phenotypic manifestations, characterized by the deficiency of lysosomal alpha mannosidase which causes accumulation of neutral oligosaccharides. Until recently, the hematopoietic stem cell transplantation was the only clinical feasible therapeutic option. Only in 2018, the European Medicines Agency's committee approved the recombinant enzyme velmanase alfa for long-term treatment of non-neurological manifestations in mild and moderate forms of alpha-mannosidosis. In this study, the very early biochemical effects of enzyme replacement therapy in in a 7-month-old patient with alpha-mannosidosis were described. Velmanase alpha was administered as supporting therapy awaiting for hematopoietic stem cell transplantation, the treatment chosen for the patient because of the early onset form. The results showed that the enzyme replacement therapy was able to reduce the content of three different mannosyl-oligosaccharides monitored by tandem mass spectrometry after 2 months of treatment. In particular, the mean relative changes from baseline values were -67% in urine and -53% in serum at the latest observation. The study also showed that the enzymatic activity detected in serum 1 week after the first infusion was four times higher than the normal values and constant in the following points of observation. These findings led us to assume that velmanase alfa might be biologically active in this young patient.

Keywords: Hematopoietic cell transplantation; alpha mannosidosis; enzyme replacement therapy; liquid chromatography coupled with tandem mass spectrometry; oligosaccharides; thin layer chromatography.

PubMed Disclaimer

Conflict of interest statement

L. S., L. Z., L. P., C. M., S. Z., A. D., R. C., T. G., and C. C. declare that they have no conflict of interest.

Figures

FIGURE 1
FIGURE 1
TLC of neutral oligosaccharides in urine (line 1,2) and serum (line 4,5) collected immediately before the first infusion (line 1, 4) and before the eighth infusion (line 2, 5) of VA. Lane 3 contains a standard mixture (Mix) with glucose, galactose, lactose and maltotetraose. Line 6 contains the internal standard (Glc7) used for LC/MS‐MS analyses
FIGURE 2
FIGURE 2
Specific TIC (Total Ion Chromatogram) of mannosyl‐OS in positive mode of urine (A1, A2) and serum (B1, B2) samples collected immediately before the first infusion (A1, B1) and before the eighth infusion of VA (A2, B2)
FIGURE 3
FIGURE 3
Relative changes of mannosyl‐OS in urine and serum from baseline values to the eighth VA infusion
See this image and copyright information in PMC

References

    1. Adam J, Malone R, Lloyd S, Lee J, Hendriksz CJ, Ramaswami U. Disease progression of alpha‐mannosidosis and impact on patients and carers—a UK natural history survey. Mol Genet Metab Rep. 2019;20:100480. - PMC - PubMed
    1. Malm D, Nilssen Ø. Alpha‐mannosidosis. Orphanet J Rare Dis. 2008;3:21. - PMC - PubMed
    1. Beck M, Olsen KJ, Wraith JE, et al. Natural history of alpha mannosidosis: a longitudinal study. Orphanet J Rare Dis. 2013;8:88 http://www.ojrd.com/content/8/1/88. - PMC - PubMed
    1. Malm D, Nilssen Ø. Alpha‐Mannosidosis. 2001 [Updated 2019 Mar 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993‐2019. https://www.ncbi.nlm.nih.gov/books/NBK1396/. - PubMed
    1. Guffon N, Tylki‐Szymanska A, Borgwardt L, et al. Recognition of alpha‐mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group. Mol Genet Metab. 2019;126:470‐474. - PubMed

Publication types