Advertisement

Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III

  • 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
  • Rafael ArtuchEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 25)

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.

Keywords

Inductively Couple Plasma Mass Spectrometry Pyridoxal Phosphate Genistein Treatment GAGs Excretion Coadjuvant Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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.

References

  1. 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 107:705–710CrossRefPubMedGoogle Scholar
  2. Delgadillo V, O’Callaghan MM, Artuch R, Montero R, Pineda M (2011) Genistein supplementation in patients affected by Sanfilippo disease. J Inherit Metab Dis 34:1039–1044CrossRefPubMedGoogle Scholar
  3. Kakkis ED, Muenzer J, Tiller GE et al (2001) Enzyme-replacement therapy in mucopolysaccharidoses I. N Engl J Med 334:182–188CrossRefGoogle Scholar
  4. Lu J, Frank EL (2008) Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 54:901–906CrossRefPubMedGoogle Scholar
  5. 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 37:439–446CrossRefPubMedGoogle Scholar
  6. 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 25:109–115CrossRefPubMedGoogle Scholar
  7. Moyano D, Vilaseca MA, Pineda M et al (1997) Tocopherol in inborn errors of intermediary metabolism. Clin Chim Acta 263:147–155CrossRefPubMedGoogle Scholar
  8. Navas P, Villalba JM, de Cabo R (2007) The importance of plasma membrane coenzyme Q in aging and stress responses. Mitochondrion 7S:34–40CrossRefGoogle Scholar
  9. 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 3421–3452Google Scholar
  10. 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 94:173–177CrossRefPubMedGoogle Scholar
  11. 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 14:846–852CrossRefPubMedGoogle Scholar
  12. Roberts AL, Howarth GS, Liaw WC et al (2009) Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA. J Cell Physiol 219:259–264CrossRefPubMedGoogle Scholar
  13. Sohal RS (2004) Coenzyme Q and vitamin E interactions. Methods Enzymol 378:146–151CrossRefPubMedGoogle Scholar
  14. 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 22:7–24PubMedGoogle Scholar
  15. 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–S49CrossRefPubMedGoogle Scholar
  16. 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 1279:99–108CrossRefPubMedGoogle Scholar
  17. 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 102:462–470CrossRefPubMedPubMedCentralGoogle Scholar
  18. Willis R, Anthony M, Sun L, Honse Y, Qiao G (1999) Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status. Biofactors 9:359–363CrossRefPubMedGoogle Scholar
  19. 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 144:581–588CrossRefPubMedGoogle Scholar
  20. Yogalingam G, Hopwood JJ (2001) Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: diagnostic, clinical, and biological implications. Hum Mutat 18:264–281CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Dèlia Yubero
    • 1
  • Raquel Montero
    • 1
    • 3
  • Mar O’Callaghan
    • 1
  • Mercè Pineda
    • 1
  • Silvia Meavilla
    • 1
  • Veronica Delgadillo
    • 1
  • Cristina Sierra
    • 1
  • Laura Altimira
    • 1
  • Plácido Navas
    • 3
    • 4
  • Simon Pope
    • 5
  • Marcus Oppenheim
    • 5
  • Viruna Neergheen
    • 5
  • Arunabha Ghosh
    • 6
  • Phillipa Mills
    • 7
  • Peter Clayton
    • 7
  • Emma Footitt
    • 7
  • Maureen Cleary
    • 7
  • Iain Hargreaves
    • 5
  • Simon A. Jones
    • 6
  • Simon Heales
    • 2
    • 5
    • 7
  • Rafael Artuch
    • 1
    • 3
    Email author
  1. 1.Clinical Chemistry, Gastroenterology and Neurology DepartmentsHospital Sant Joan de DéuBarcelonaSpain
  2. 2.Chemical Pathology, Great Ormond Street HospitalLondonUK
  3. 3.Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)Instituto de Salud Carlos IIIMadridSpain
  4. 4.Centro Andaluz de Biología del DesarrolloUniversidad Pablo de Olavide-CSIC-JASevillaSpain
  5. 5.Neurometabolic Unit, National HospitalLondonUK
  6. 6.Willink Unit, Manchester Centre for Genomic Medicine, CMFTUniversity of ManchesterManchesterUK
  7. 7.Genetics and Genomic MedicineUCL Institute of Child HealthLondonUK

Personalised recommendations