Abstract
Despite their good appetite, many females with Rett syndrome (RTT) meet the criteria for moderate to severe malnutrition. Although feeding difficulties may play a part in this, other constitutional factors such as altered metabolic processes are suspected. Irregular breathing is a common clinical feature, leading to chronic respiratory alkalosis or acidosis. We assumed that these changes in intracellular pH cause disturbances in the metabolic equilibrium, with important nutritional consequences. The study population consisted of a group of thirteen well-defined RTT girls with extended clinical, molecular and neurophysiological assessments. Despite normal levels of total dietary energy and protein intakes, malnutrition was confirmed based on significantly low fat-free mass index (FFMI) values. Biochemical screening of multiple metabolic pathways showed significantly elevated plasma creatine concentrations and increased urinary creatine/creatinine ratio in five RTT girls. Four girls, 10 years and older, were forceful breathers, one 13-year-old girl had an undetermined cardiorespiratory phenotype. An isolated increase of the urinary creatine/creatinine ratio was seen in two girls, a 9-year old forceful and a 4-year old feeble breather. Given that the young girls are feeble breathers and the older girls are forceful breathers, it is impossible to determine whether the elevated creatine concentrations are due to increasing age or cardiorespiratory phenotype. Furthermore, MeCP2 deficiency may cause epigenetic aberrations affecting the expression of the creatine-transporter gene, which is located at Xq28. Further studies are required to confirm these findings and to provide greater insight into the pathogenesis of the abnormal creatine metabolism in RTT.
Trial registration number (www.clinicaltrials.gov): 00786071
Competing interests: None declared.
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Abbreviations
- BMI:
-
Body mass index
- FFM:
-
Fat-free mass
- FFMI:
-
Fat-free mass index
- ID:
-
Intellectual disability
- MECP2 :
-
Methyl CpG binding protein 2 gene
- MeCP2:
-
Methyl CpG binding protein 2
- RTT:
-
Rett syndrome
- SD:
-
Standard deviation
- TBW:
-
Total body water
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Acknowledgments
The authors would like to thank the RTT girls and their parents for participating in this project. Furthermore, we would like to thank the ESRRA group (European Scientific Rett Research Association; Mrs Flora Apartopoulos, Dr Robert S Delamont, Dr Stig Hansen, Mr Elias Keter, Mrs Märith Bergström-Isacsson, Dr Bengt Engerström, Dr Lars Engerström, Mrs Gunilla Larsson, Dr Stefania Bigoni, Dr Giorgio Pini and Dr Sami SF Al-Rawas), Dr. Alison Kerr, and Dr. Dick van Waardenburg for their support and advice.
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Communicated by: Carlo Dionisi-Vici.
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Synopsis
A striking increase in creatine concentration was observed in the body fluids of females with Rett syndrome, which may reflect the altered carbon dioxide metabolism of these girls or their impaired nutritional status or both.
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The article has not been and will not be published elsewhere in substantially the same form. The article has been circulated and final approval of the version to be peer-reviewed was secured from all co-authors prior to article submission. This includes confirmation of absence of previous similar or simultaneous publications their inspection of the manuscript, their substantial contribution to the work, and their agreement to submission.
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Nicky S.J. Halbach: involvement in conception and design analysis and interpretation of data and drafting the article.
Eric E.J. Smeets: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Jörgen Bierau: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Irene M.L.W. Keularts: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Guy Plasqui: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Peter O.O. Julu: involvement in analysis and interpretation of data and revising the article critically for important intellectual content.
Ingegerd Witt Engerström: involvement in analysis and interpretation of data and revising the article critically for important intellectual content.
Jaap A. Bakker: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Leopold M.G. Curfs: involvement in conception and design analysis and interpretation of data and revising the article critically for important intellectual content.
Guarantor for the article: Leopold M.G. Curfs.
Details of funding: the authors confirm independence from the sponsors the content of the article has not been influenced by the sponsors.
Details of ethics approval: ethical approval was obtained from the Medical Ethical Committee at the Maastricht University Medical Centre (MEC 08-2-119) and all parents provided informed written consent. The study was registered at clinicaltrials.gov.
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Halbach, N.S.J. et al. (2011). Altered Carbon Dioxide Metabolism and Creatine Abnormalities in Rett Syndrome. In: JIMD Reports - Case and Research Reports, 2011/3. JIMD Reports, vol 3. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_76
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DOI: https://doi.org/10.1007/8904_2011_76
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