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Journal of Genetic Counseling

, Volume 25, Issue 5, pp 936–944 | Cite as

Impaired Health-Related Quality of Life in Children and Families Affected by Methylmalonic Acidemia

  • Kimberly Splinter
  • Anna-Kaisa Niemi
  • Rachel Cox
  • Julia Platt
  • Monisha Shah
  • Gregory M. Enns
  • Mureo Kasahara
  • Jonathan A. Bernstein
Original Research

Abstract

An understanding of health related quality of life (HRQoL) in children and families affected by methylmalonic acidemia (MMA) is important in planning counseling and therapeutic intervention. Liver transplantation (LT) is used as a treatment for MMA; however, its risks and benefits continue to be investigated. The purpose of this study was twofold: (1) to measure HRQoL in children and families affected by MMA using the Pediatric Quality of Life Inventory (PedsQL™) parent version, and (2) to assess the impact of LT on HRQoL by comparing LT and non-LT patient scores and free responses. Parents/caregivers reported lower scores on the majority of the PedsQL™ scales as compared to samples of healthy children, children with solid organ transplants for indications other than MMA, and families affected by chronic conditions. Scores for children with MMA were lowest in school and social functioning and scores for families were lowest in worry and activity impairment. There were no significant differences in LT and non-LT patient scores on the PedsQL™ scales. Our results document the negative impact of MMA on HRQoL.

Keywords

Methylmalonic acidemia Health-related quality of life Inborn error of metabolism Liver transplantation 

Notes

Acknowledgments

The authors sincerely thank the OAA for help in recruiting families. The authors also thank the Mapi Research Trust (Lyon, France; email: PROinformation@mapi-trust.org; website: www.pedsql.org) for permission to use the PedsQL™ Inventory (Copyright 1998 JW Varni, Ph.D. All rights reserved).

Compliance with Ethical Standards

Conflict of Interest

Kimberly Splinter, Anna-Kaisa Niemi, Rachel Cox, Julia Platt, Monisha Shah, Gregory M. Enns, Mureo Kasahara, and Jonathan A. Bernstein declare that they have no conflict of interest.

Human Studies and 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 (5). Informed consent was obtained from all patients for being included in the study.

Animal Studies

No animal studies were carried out by the authors for this article.

Supplementary material

10897_2015_9921_MOESM1_ESM.doc (152 kb)
ESM 1 (DOC 152 kb)

References

  1. Alonso, E. M., Limbers, C. A., Neighbors, K., Martz, K., Bucuvalas, J. C., Webb, T., et al. (2010). Cross-Sectional Analysis of Health-Related Quality of Life in Pediatric Liver Transplant Recipients. The Journal of Pediatrics, 156, 270–276.CrossRefPubMedGoogle Scholar
  2. Baumgarter, E. R., & Viardot, C. (1995). Long-Term Follow-up of 77 Patients with Isolated Methylmalonic Acidaemia. Journal of Inherited Metabolic Disease, 18, 138–142.CrossRefPubMedGoogle Scholar
  3. Burfield, J., Hussa, C., & Randall, R. (2012). Hot Topics in Metabolism. Topics in Clinical Nutrition, 27, 181–195.CrossRefGoogle Scholar
  4. Cella, D. F. (1996). Quality of Life Outcomes: Measurement and Validation. Oncology, 10, 233–246.PubMedGoogle Scholar
  5. Centers for Disease Control and Prevention (CDC). (2000). Measuring Healthy Days.Google Scholar
  6. Chakrapani, A., Sivakumar, P., McKiernan, P. J., & Leonard, J. V. (2002). Metabolic Stroke in Methylmalonic Acidemia Five Years After Liver Transplantation. The Journal of Pediatrics, 140, 261–263.CrossRefPubMedGoogle Scholar
  7. Droter, D. (1997). Relating Parent and Family Functioning to the Psychological Adjustment of Children with Chronic Health Conditions: What Have we Learned? What do we Need to Know? Journal of Pediatric Psychology, 22, 149–165.CrossRefGoogle Scholar
  8. Eminoglu, T. F., Soysal, S. A., Tumer, L., Okur, I., & Hasanoglu, A. (2013). Quality of Life in Children Treated with Restrictive Diet for Inherited Metabolic Disease. Pediatrics International, 55, 428–433.CrossRefPubMedGoogle Scholar
  9. Fabre, A., Baumstarck, K., Cano, A., Loundou, A., Berbis, J., Chabrol, B., et al. (2013). Assessment of Quality of Life of the Children and Parents Affected by Inborn Errors of Metabolism with Restricted Diet: Preliminary Results of a Cross-Sectional Study. Health and Quality of Life Outcomes, 11, 158.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hatzmann, J., Valstar, M. J., Bosch, A. M., Wijburg, F. A., Heymans, H. S., & Grootenhius, M. A. (2009). Predicting Health-Related Quality of Life of Parents of Children with Inherited Metabolic Diseases. Acta Paediatrica, 98, 205–1210.CrossRefGoogle Scholar
  11. Heidenreich, R., Natowicz, M., Hainline, B. E., Berman, P., Kelley, R. I., Hillman, R. E., et al. (1988). Acute Extrapyramidal Syndrome in Methylmalonic Acidemia- Metabolic Stroke Involving the Globus Pallidus. The Journal of Pediatrics, 113, 1022–1027.CrossRefPubMedGoogle Scholar
  12. Holmbeck, G. N., Westhoven, V. C., Phillips, W. S., Bowers, R., Gruse, C., Nikolopoulos, T., et al. (2003). A Multimethod, Multi-Informant, and Multidimensional Perspective on Psychosocial Adjustment in Preadolescents with Spina Bifida. Journal of Consulting and Clinical Psychology, 71, 782–796.CrossRefPubMedGoogle Scholar
  13. Horster, F., Baumgartner, M., Viardot, C., Suormala, T., Burgard, P., Fowler, B., et al. (2007). Long-Term Outcome in Methylmalonic Acidurias is Influenced by the Underlying Defect (mut0, mut-, cblA, cblB). Pediatric Research, 62, 225–230.CrossRefPubMedGoogle Scholar
  14. Horster, F., & Hoffmann, G. F. (2004). Pathophysiology, Diagnosis, and Treatment of Methylmalonic Aciduria-Recent Advances and new Challenges. Pediatric Nephrology, 19, 1071–1074.CrossRefPubMedGoogle Scholar
  15. Kaplan, P., Ficicioglu, C., Mazur, A. T., Palmieri, M. J., & Berry, G. T. (2006). Liver Transplantation is not Curative for Methylmalonic Acidopathy Caused by Methylmalonyl-CoA Mutase Deficiency. Molecular Genetics and Metabolism, 88, 322–326.CrossRefPubMedGoogle Scholar
  16. Kasahara, M., Horikawa, R., Tagawa, M., Uemoto, S., Yokoyama, S., & Shibata, Y. (2006). Current Role of Liver Transplantation for Methylmalonic Acidemia: A Review of the Literature. Pediatric Transplantation, 10, 943–947.CrossRefPubMedGoogle Scholar
  17. Kayler, L. K., Merion, R. M., Lee, S., Sung, R. S., Punch, J. D., & Rudich, S. M. (2002). Long-Term Survival After Liver Transplantation in Children with Metabolic Disorders. Pediatric Transplantation, 6, 295–300.CrossRefPubMedGoogle Scholar
  18. Leonard, J. V. (1995). The Management and Outcome of Propionic and Methylmalonic Acidaemia. Journal of Inherited Metabolic Disease, 18, 430–434.CrossRefPubMedGoogle Scholar
  19. Matsui, S. M., Mahoney, M. J., & Rosenberg, L. E. (1983). The Natural History of the Inherited Methylmalonic Acidemias. New England Journal of Medicine, 308, 857–861.CrossRefPubMedGoogle Scholar
  20. McGuire, P. J., Lim-Melia, E., Diaz, G. A., Raymond, K., Larkin, A., Wasserstein, M. P., et al. (2008). Combined Liver-Kidney Transplant for the Management of Methylmalonic Aciduria: A Case Report and Review of the Literature. Molecular Genetics and Metabolism, 93, 22–29.CrossRefGoogle Scholar
  21. Molteni, K. H., Oberley, T. D., Wolff, J. A., & Friedman, A. L. (1991). Progressive Renal Insufficiency in Methylmalonic Acidemia. Pediatric Nephrology, 5, 323–326.CrossRefPubMedGoogle Scholar
  22. Morioka, D., Kasahara, M., Horiokawa, R., Yokoyama, S., Fukuda, A., & Nakagawa, A. (2007). Efficacy of Living Donor Liver Transplantation for Patients with Methylmalonic Acidemia. American Journal of Transplantation, 7, 2782–2787.CrossRefPubMedGoogle Scholar
  23. Morioka, D., Kasahara, M., Takada, Y., Shirouzu, Y., Taira, K., Sakamoto, S., et al. (2005). Current Role of Liver Transplantation for the Treatment of Urea Cycle Disorders: A Review of the Worldwide English Literature and 13 Cases at Kyoto University. Liver Transplant, 11, 1332–1342.CrossRefGoogle Scholar
  24. Nagarajan, S., Enns, G. M., Millan, M. T., Winter, S., & Sarwal, M. M. (2005). Management of Methylmalonic Acidaemia by Combined Liver-Kidney Transplantation. Journal of Inherited Metabolic Disease, 28, 517–524.CrossRefPubMedGoogle Scholar
  25. Nicolaides, P., Leonard, J., & Surtees, R. (1998). Neurological Outcomes of Methylmalonic Acidaemia. Archives of Disease in Childhood, 78, 508–512.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Niemi, A. K., Kim, I. K., Krueger, C. E., Cowan, T. M., Baugh, N., Farrell, R., et al. (2015). Treatment of Methylmalonic Acidemia by Liver or Combined Liver-Kidney Transplantation. The Journal of Pediatrics, 116, 1455–1461.CrossRefGoogle Scholar
  27. Nyhan, W. L., Gargus, J. J., Boyle, K., Selby, R., & Koch, R. (2002). Progressive Neurologic Disability in Methylmalonic Acidemia Despite Transplantation of the Liver. European Journal of Pediatrics, 161, 377–379.CrossRefPubMedGoogle Scholar
  28. Oberholzer, V.G., Levin, B., & Burgess, E.A. (1967). Methylmalonic aciduria. An inborn error of metabolism leading to chronic metabolic acidosis. Arch Dis Child, 42, 492–504.Google Scholar
  29. Palermo, T. M., Long, A. C., Lewandowski, A. S., Drotar, D., Quittner, A. L., & Walker, L. S. (2008). Evidence-Based Assessment of Health-Related Quality of Life and Functional Impairment in Pediatric Psychology. Journal of Pediatric Psychology, 33, 983–996.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Perito, E. R., Rhee, S., Roberts, J. P., & Rosenthal, P. (2014). Pediatric Liver Transplantation for Urea Cycle Disorders and Organic Acidemias: United Network for Organ Sharing Data for 2002–2012. Liver Transplant, 20, 89–99.CrossRefGoogle Scholar
  31. Schmidt, S., Petersen, C., & Bullinger, M. (2003). Coping with Chronic Disease from the Perspective of Children and Adolescents- a Conceptual Framework and its Implications for Participation. Child: Care, Health and Development, 29, 63–75.Google Scholar
  32. Seid, M., Varni, J. W., Rode, C. A., & Katz, E. R. (1999). The Pediatric Cancer Quality of Life Inventory: A Modular Approach to Measuring Health-Related Quality of Life in Children with Cancer. International Journal of Cancer. Supplement, 12, 71–76.CrossRefGoogle Scholar
  33. Shneider, B. L., Vockley, J., & Mazariegos, G. V. (2011). Trading Places: Liver Transplantation as a Treatment, not a Cure, for Metabolic Liver Disease. Liver Transplant, 17, 628–630.CrossRefGoogle Scholar
  34. Spieth, L. E., & Harris, C. V. (1996). Assessment of Health-Related Quality of Life in Children and Adolescents: An Integrative Review. Journal of Pediatric Psychology, 21, 175–193.CrossRefPubMedGoogle Scholar
  35. Stokke, O., Eldjarn, L., Norum, K. R., Steen-Johnson, J., & Halvorsen, S. (1967). Methylmalonic Acidemia: A new Inborn Error of Metabolism Which may Cause Fatal Acidosis in the Neonatal Period. Scandinavian Journal of Clinical and Laboratory Investigation, 20, 313–328.CrossRefGoogle Scholar
  36. Strauss, A. L., & Corbin, J. M. (1998). Open coding. In A. L. Strauss, & J. M. Corbin (Eds.), Basics of qualitative research (pp. 101–121). Thousand Oaks: SAGE Publications, Inc.Google Scholar
  37. Suormala, T., Baumgartner, M. R., Coelho, D., Zavadakova, P., Kozich, V., Koch, H. G., et al. (2004). The cblD Defect Causes Either Isolated or Combined Deficiency of Methylcobalamin and Adenosylcobalamin Synthesis. Journal of Biochemistry, 279, 42742–42749.Google Scholar
  38. van der Meer, S. B., Poggi, F., Spada, M., Bonnefont, J. P., Ogier, H., Hubert, P., et al. (1994). Clinical Outcome of Long-Term Management of Patients with Vitamin B12-Unresponsive Methylmalonic Acidemia. The Journal of Pediatrics, 125, 903–908.CrossRefPubMedGoogle Scholar
  39. van’t Hoff, W., McKiernan, P. J., Surtees, R. A. H., & Leonard, J. V. (1999). Liver Transplantation for Methylmalonic Acidaemia. European Journal of Pediatrics, 158, S70–S74.CrossRefPubMedGoogle Scholar
  40. van’t Hoff, W. G., Dixon, M., Taylor, J., Mistry, P., Rolles, K., Rees, L., et al. (1998). Combined Liver-Kidney Transplantation in Methylmalonic Acidemia. The Journal of Pediatrics, 132, 1043–1044.CrossRefGoogle Scholar
  41. Varni, J.W., Seid, M., & Kurtin, P.S. (2001). PedsQL 4.0: reliability and validity of Pediatric Quality of Life Inventory version 4.0 generic core scales in health and patient populations. Med Care, 39, 800–812.Google Scholar
  42. Varni, J. W., Sherman, S. A., Burwinkle, T. M., Dickinson, P. E., & Dixon, P. (2004). The PedsQL Family Impact Module: Preliminary Reliability and Validity. Health and Quality of Life Outcomes, 2, 55.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Weissberg-Benchell, J., Zielinski, T. E., Rodgers, S., Greenley, R. N., Askenazi, D., Goldstein, S. L., et al. (2010). Pediatric Health-Related Quality of Life: Feasibility, Reliability and Validity of the PedsQL Transplant Module. American Journal of Transplantation, 10, 1677–1685.CrossRefPubMedGoogle Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2015

Authors and Affiliations

  • Kimberly Splinter
    • 1
    • 2
  • Anna-Kaisa Niemi
    • 3
    • 4
  • Rachel Cox
    • 3
  • Julia Platt
    • 3
  • Monisha Shah
    • 3
  • Gregory M. Enns
    • 3
  • Mureo Kasahara
    • 5
  • Jonathan A. Bernstein
    • 3
  1. 1.Department of GeneticsStanford University School of MedicineStanfordUSA
  2. 2.Department of Biomedical InformaticsHarvard Medical SchoolBostonUSA
  3. 3.Department of Pediatrics, Division of Medical Genetics, Stanford Children’s HospitalStanford UniversityStanfordUSA
  4. 4.Department of Pediatrics, Division of Neonatal and Developmental MedicineStanford UniversityStanfordUSA
  5. 5.Transplantation CenterNational Center for Child Health and DevelopmentTokyoJapan

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