Abstract
Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiencies of lysosomal enzymes catalyzing degradation of glycosaminoglycans (GAGs). Previously, we reported a secondary plasma coenzyme Q10 (CoQ) deficiency in MPS patients. For this study, nine MPS patients were recruited in the Hospital Sant Joan de Déu (HSJD, Barcelona) and two patients in the Neurometabolic Unit, National Hospital (NMU, London), to explore the nutritional status of MPS type III patients by analyzing several vitamins and micronutrients in blood and in cerebrospinal fluid. Plasma CoQ and plasma and cerebrospinal fluid pyridoxal phosphate (PLP) content were analyzed by high-pressure liquid chromatography (HPLC) with electrochemical and fluorescence detection, respectively. We found that most MPS-III patients disclosed low plasma pyridoxal phosphate (PLP) values (seven out of nine) and also low plasma CoQ concentrations (eight out of nine). We observed significantly lower median values of PLP, tocopherol, and CoQ (Mann–Whitney U test, p = 0.006, p = 0.004, and p = 0.001, respectively) in MPS patients when compared with age-matched controls. Chi-square test showed a significant association between the fact of having low plasma PLP and CoQ values in the whole cohort of patients. Cerebrospinal fluid PLP values were clearly deficient in the two patients studied. In conclusion, we report a combined CoQ and PLP deficiency in MPS-III patients. These observations could be related to the complexity of the physiopathology of the disease. If our results are confirmed in larger series of patients, CoQ and PLP therapy could be trialed as coadjuvant therapy with the current MPS treatments.
Competing interests: None declared
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References
de Ruijter J, de Ru MH, Wagemans T et al (2012) Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III. Mol Genet Metab 107:705–710
Delgadillo V, O’Callaghan MM, Artuch R, Montero R, Pineda M (2011) Genistein supplementation in patients affected by Sanfilippo disease. J Inherit Metab Dis 34:1039–1044
Kakkis ED, Muenzer J, Tiller GE et al (2001) Enzyme-replacement therapy in mucopolysaccharidoses I. N Engl J Med 334:182–188
Lu J, Frank EL (2008) Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 54:901–906
Matalonga L, Arias A, Coll MJ, Garcia-Villoria J, Gort L, Ribes A (2014) Treatment effect of coenzyme Q(10) and an antioxidant cocktail in fibroblasts of patients with Sanfilippo disease. J Inherit Metab Dis 37:439–446
Montero R, Artuch R, Briones P et al (2005) Muscle coenzyme Q10 concentrations in patients with probable and definite diagnosis of respiratory chain disorders. Biofactors 25:109–115
Moyano D, Vilaseca MA, Pineda M et al (1997) Tocopherol in inborn errors of intermediary metabolism. Clin Chim Acta 263:147–155
Navas P, Villalba JM, de Cabo R (2007) The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion 7S:34–40
Neufeld EF, Muenzer J (2001) The mucopolysaccharidoses. In: Scriver CR, Beauder AL, Sly WS et al (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York, pp 3421–3452
Ormazabal A, Oppenheim M, Serrano M et al (2008) Pyridoxal 5′-phosphate values in cerebrospinal fluid: reference values and diagnosis of PNPO deficiency in paediatric patients. Mol Genet Metab 94:173–177
Piotrowska E, Jakóbkiewicz-Banecka J, Baranska S et al (2006) Genistein-mediated inhibition of glycosaminoglycan synthesis as a basis for gene expression-targeted isoflavone therapy for mucopolysaccharidoses. Eur J Hum Genet 14:846–852
Roberts AL, Howarth GS, Liaw WC et al (2009) Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA. J Cell Physiol 219:259–264
Sohal RS (2004) Coenzyme Q and vitamin E interactions. Methods Enzymol 378:146–151
Spinneker A, Sola R, Lemmen V, Castillo MJ, Pietrzik K, González-Gross M (2007) Vitamin B6 status, deficiency and its consequences--an overview. Nutr Hosp 22:7–24
Tondo M, Lambruschini N, Gomez-Lopez L et al (2010) The monitoring of trace elements in blood samples from patients with inborn errors of metabolism. J Inherit Metab Dis 33(Suppl 3):S43–S49
Villani GR, Di Domenico C, Musella A, Cecere F, Di Napoli D, Di Natale P (2009) Mucopolysaccharidosis IIIB: oxidative damage and cytotoxic cell involvement in the neuronal pathogenesis. Brain Res 1279:99–108
Wijburg FA, Węgrzyn G, Burton BK, Tylki-Szymańska A (2013) Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr 102:462–470
Willis R, Anthony M, Sun L, Honse Y, Qiao G (1999) Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. Biofactors 9:359–363
Wraith JE, Clarke LA, Beck M et al (2004) Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-l-iduronidase (Iaronidase). J Pediatr 144:581–588
Yogalingam G, Hopwood JJ (2001) Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: diagnostic, clinical, and biological implications. Hum Mutat 18:264–281
Acknowledgments
This research was partially funded by grants PI11/02350, PI11/00078, PI1400028, and PI14-01962 from the Spanish Ministry of Health (Fondo de Investigación Sanitaria, Instituto de Salud Carlos III). We are very grateful for the support of the “MPS España” association.
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Communicated by: Marc Patterson
Appendices
Synopsis
Combined CoQ and PLP deficiency is common in MPS-III patients.
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Conflict of Interest
Dèlia Yubero, Raquel Montero, Mar O’Callaghan, Mercè Pineda, Silvia Meavilla, Veronica Delgadillo, Cristina Sierra, Laura Altimira, Plácido Navas, Simon Pope, Marcus Oppenheim, Viruna Neergheen, Arunabha Ghosh, Phillipa Mills, Peter Clayton, Emma Footitt, Maureen Cleary, Iain Hargreaves, Simon A. Jones, Simon Heales, and Rafael Artuch declare that they have no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. Informed consent was obtained and must be available upon request.
Author Contributions
All co-authors have peer-reviewed the manuscript and there is a consensus agreement to submission. Thus, we confirm the absence of previous similar and simultaneous publications. Dr. Yubero, Montero, O’Callaghan, Heales, and Artuch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
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Study concept and design: Yubero, Montero, O’Callaghan, Pineda, Hargreaves, Heales, and Artuch
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Acquisition of data: Yubero, Montero, O’Callaghan, Pineda, Meavilla, Delgadillo, Sierra, Altimira, Pope, Oppenheim, Neergheen, Ghosh, Mills, Clayton, Footitt, Cleary, Jones, and Heales
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Analysis and interpretation of data: Yubero, Montero, O’Callaghan, Navas, Mills, Clayton, Hargreaves, Heales, and Artuch
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Drafting of the manuscript: All authors
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Critical revision of the manuscript for important intellectual content: All authors
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Study supervision: Artuch
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Yubero, D. et al. (2015). Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III. 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_421
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DOI: https://doi.org/10.1007/8904_2015_421
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