Abstract
Background: It has been suggested, on a few GSD1b patients, that vitamin E improves neutrophil count and reduces frequency and severity of infections.
The main objective of the present study was to investigate the efficacy of vitamin E on the neutropenia, neutrophil dysfunction and IBD in the entire Italian caseload of GSD1b patients.
Patients and methods: Eighteen GSD1b patients, median age at the time of the study protocol 14.5 (range, 0.6–42 years), were enrolled from four Italian referral centres for metabolic diseases. For the evaluation of the efficacy of vitamin E, neutrophil count and function, frequency of infections needing hospitalization and inflammatory bowel activity were evaluated periodically all over one year before and during vitamin E therapy.
Results: Frequency (1.5 ± 0.1 vs. 6.0 ± 0.6, p = 0.003) and severity of infections (2.2 ± 0.2 vs. 3.7 ± 0.4, p = 0.003) were lower and mean value of neutrophil count (1,583 ± 668 vs. 941 ± 809, p = 0.03) higher during vitamin E supplementation. Neutrophil function results improved during vitamin supplementation. PCDAI showed a significant reduction in the inflammatory activity during vitamin E supplementation (9 ± 1.4 vs. 13 ± 1.2, p = 0.006). In seven patients G-CSF requirement decreased and the dose was reduced after the end of the study.
In conclusion, our study demonstrated the efficacy of vitamin E supplementation. Vitamin E has evident advantages as compared to G-CSF, as it can be assumed orally, and it has not been associated with severe side effects.
Competing interests: None declared
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References
Chou JY, Jun HS, Mansfield BC (2010) Neutropenia in type Ib glycogen storage disease. Curr Opin Hematol 17:36–42
De la Fuente M, Ferrández MD, Burgos MS, Soler A, Prieto A, Miquel J (1998) Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 76:373–380
Gorman AM, Healy SJ, Jäger R, Samali A (2012) Stress management at the ER: regulators of ER stress-induced apoptosis. Pharmacol Ther 134:306–316
Guionie O, Clottes E, Stafford K, Burchell A (2003) Identification and characterization of new human glucose-6-phosphatase isoform. FEBS Lett 551:159–164
Jun HS, Weinstein DA, Lee YM, Mansfield BC, Chou JY (2014) Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib. Blood 123:2843–2853
Kim SY, Nguyen AD, Gao JL, Murphy PM, Mansfield BC, Chou JY (2006) Bone marrow-derived cells require a functional glucose-6-phosphate transporter for normal myeloid functions. J Biol Chem 281:28794–28801
Kim SY, Jun HS, Mead PA, Mansfield BC, Chou JY (2008) Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type 1b. Blood 111:5704–5711
Kuijpers TW, Maianski NA, Tool AT, Smit GP, Rake JP, Roos D, Visser G (2003) Apoptotic neutrophils in the circulation of patients with glycogen storage disease type 1b (GSD1b). Blood 101:5021–5024
Kulkarni SS, Cary LH, Gambles K, Hauer-Jensen M, Kumar KS, Ghosh SP (2012) Gamma-tocotrienol, a radiation prophylaxis agent, induces high levels of granulocyte colony-stimulating factor. Int Immunopharmacol 14:495–503
Leuzzi R, Bánhegyi G, Kardon T, Marcolongo P, Capecchi PL, Burger HJ, Benedetti A, Fulceri R (2003) Inhibition of microsomal glucose-6-phosphate transport in human neutrophils results in apoptosis: a potential explanation for neutrophil dysfunction in glycogen storage disease type 1b. Blood 101:2381–2387
Melis D, Parenti G, Della Casa R, Sibilio M, Berni Canani R, Terrin G, Cucchiara S, Andria G (2003) Crohn’s-like ileo-colitis in patients affected by glycogen storage disease Ib: two years’ follow-up of patients with a wide spectrum of gastrointestinal signs. Acta Paediatr 92:1415–1421
Melis D, Fulceri R, Parenti G, Marcolongo P, Gatti R, Parini R, Riva E, Della Casa R, Zammarchi E, Andria G, Benedetti A (2005) Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature. Eur J Pediatr 164:501–508
Melis D, Della Casa R, Parini R, Rigoldi M, Cacciapuoti C, Marcolongo P, Benedetti A, Gaudieri V, Andria G, Parenti G (2009) Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b. Eur J Pediatr 168:1069–1074
Pinsk M, Burzynski J, Yhap M, Fraser RB, Cummings B, Ste-Marie M (2002) Acute myelogenous leukemia and glycogen storage disease 1b. J Pediatr Hematol Oncol 24:756–758
Seidner DL, Lashner BA, Brzezinski A, Banks PL, Goldblum J, Fiocchi C, Katz J, Lichtenstein GR, Anton PA, Kam LY, Garleb KA, Demichele SJ (2005) An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial. Clin Gastroenterol Hepatol 3:358–369
Singh VK, Brown DS, Kao TC (2009) Tocopherol succinate: a promising radiation countermeasure. Int Immunopharmacol 9:1423–1430
Ventura MT, Serlenga E, Tortorella C, Antonaci S (1994) In vitro vitamin E and selenium supplementation improves neutrophil-mediated functions and monocyte chemoattractant protein-1 production in the elderly. Cytobios 77:225–232
Visser G, Rake JP, Fernandes J, Labrune P, Leonard JV, Moses S, Ullrich K, Smit GP (2000) Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European Study on Glycogen Storage Disease type I. J Pediatr 137:187–191
Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K, Wendel U, Smit GP (2002) European Study on Glycogen Storage Disease Type I. Consensus guidelines for management of glycogen storage disease type 1b -European Study on Glycogen Storage Disease Type 1. Eur J Pediatr 161(Suppl 1):S120–S123
Visser G, de Jager W, Verhagen LP, Smit GP, Wijburg FA, Prakken BJ, Coffer PJ, Buitenhuis M (2012) Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients. J Inherit Metab Dis 35:287–300
Acknowledgement
The study was partially supported by the Italian Agency of Drugs (AIFA). Study protocol n. FARM5S3JT5
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Communicated by: Anita MacDonald, PhD, BSc
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Take-Home Message
Vitamin E supplementation improves clinical outcome of GSD1b patients and allows a G-CSF dose reduction with consequent reduction of G-CSF-related side effects.
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We underline that: there are no prior publications or submissions with any overlapping information; the work is not and will not be submitted to any other journal while under consideration by JIMD; there are no potential conflicts of interest, real or perceived; Dr. D. Melis wrote the first draft of the manuscript and gave substantial contributions to conception and design, acquisition of data and analysis and interpretation of data; and neither an honorarium or grant or other forms of payment were given to anyone to produce the manuscript. All the authors listed on the manuscript take full responsibility for the manuscript; moreover, Dr. D. Casa, G. Minopoli, F. Balivo, G. Parenti, S. Paci and C. Dionisi-Vici gave substantial contributions to conception and design, acquisition of data and analysis and interpretation of data, revised the manuscript critically for important intellectual content, approved the submission of this version of the manuscript and take full responsibility for the manuscript. Dr. Marcolongo and Prof. Benedetti performed the biochemical investigation, namely, the neutrophil function test; gave substantial contributions to conception and design, acquisition of data and analysis and interpretation of data; revised the manuscript critically for important intellectual content; approved the submission of this version of the manuscript; and take full responsibility for the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Prof. Generoso Andria and Giancarlo Parenti gave substantial contribution to conception and design, acquisition of data and analysis and interpretation of data and critically revised the manuscript.
Daniela Melis, Giorgia Minopoli, Francesca Balivo, Paola Marcolongo, Rossella Parini, Sabrina Paci, Carlo Dionisi-Vici, Roberto Della Casa, Angelo Benedetti, Generoso Andria and Giancarlo Parenti declare that they have no conflict of interest.
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Melis, D. et al. (2015). Vitamin E Improves Clinical Outcome of Patients Affected by Glycogen Storage Disease Type Ib. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 25. JIMD Reports, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_461
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DOI: https://doi.org/10.1007/8904_2015_461
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