Abstract
Background:
Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once.
Methods:
We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging.
Results:
During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5–6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay.
Conclusion:
NaHB is a highly effective and safe treatment that needs further controlled studies.
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Acknowledgements
We thank André Schaller for help with the interpretation of the genetic data, Mary Butz-Myrick for critical reading of the manuscript (English), and Silvan Schmidhalter for help in preparing the figures. We thank our young patient and his family for their great effort of collaboration. Part of this study was presented at the German APS meeting in Fulda, spring 2012 and previously published as an abstract for the SSIEM Symposium in Birmingham, September 2012. Mutation analysis of the ETF A&B and ETFDH genes was done by the laboratory Medizinisch Genetisches Zentrum (MGZ), Munich, Germany.
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Gautschi, M., Weisstanner, C., Slotboom, J. et al. Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy. Pediatr Res 77, 91–98 (2015). https://doi.org/10.1038/pr.2014.154
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DOI: https://doi.org/10.1038/pr.2014.154
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