Abstract
We report the major diagnostic challenge in a female patient with signs and symptoms suggestive of an early-onset mitochondrial encephalopathy. Motor and cognitive development was severely delayed and brain MRI showed signal abnormalities in the putamen and caudate nuclei. Metabolic abnormalities included 3-methylglutaconic aciduria and elevated lactate levels in plasma and cerebrospinal fluid, but were transient. Whole exome sequencing at the age of 25 years finally revealed compound heterozygous mutations c.[229G>C];[563C>T], p.[Glu77Gln];[Ala188Val] in the ECHS1 gene. Activity of short-chain enoyl-CoA hydratase, a mitochondrial enzyme encoded by the ECHS1 gene, was markedly decreased in lymphocytes. Retrospective urine analysis confirms that elevated levels of S-(2-carboxypropyl)cysteamine, S-(2-carboxypropyl)cysteine, and N-acetyl-S-(2-carboxypropyl)cysteine can be a diagnostic clue in the disease spectrum of ECHS1 mutations.
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Acknowledgements
We thank Dr. Alberto Burlina (University of Padua, Italy) for providing a urine sample from a previously reported ECHS1 case for comparison.
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Communicated by: Robin Lachmann, PhD FRCP
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Take-Home Message
Elevated levels of S-(2-carboxypropyl)cysteamine, S-(2-carboxypropyl)cysteine, and N-acetyl-S-(2-carboxypropyl)cysteine can be a diagnostic clue towards the disease spectrum of ECHS1 mutations in patients with an early-onset and severe mitochondrial encephalopathy who may survive into adulthood and have transient metabolic abnormalities including 3-methylglutaconic aciduria and elevated lactate levels in plasma and cerebrospinal fluid.
Contributions of Individual Authors
Irene C. Huffnagel: study design, data interpretation, writing manuscript.
Dr. Redeker: analysis and interpretation of genomic array data, critical revision of manuscript for intellectual content.
Dr. Reneman: MRI analysis, critical revision of manuscript for intellectual content.
Dr. Vaz: metabolite analysis, data analysis and interpretation, critical revision of manuscript for intellectual content.
Dr. Ferdinandusse: metabolite analysis, data analysis and interpretation, critical revision of manuscript for intellectual content.
Prof. Dr. Poll-The: study concept, design and supervision, patient care, data interpretation, writing manuscript.
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Prof Dr. Bwee Tien Poll-The, MD, PhD (corresponding author).
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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Irene C. Huffnagel, Egbert J. W. Redeker, Liesbeth Reneman, Frédéric M. Vaz, Sacha Ferdinandusse, and Bwee Tien Poll-The declare that they have no conflict of interest.
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Huffnagel, I.C., Redeker, E.J.W., Reneman, L., Vaz, F.M., Ferdinandusse, S., Poll-The, B.T. (2017). Mitochondrial Encephalopathy and Transient 3-Methylglutaconic Aciduria in ECHS1 Deficiency: Long-Term Follow-Up. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 39. JIMD Reports, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_48
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DOI: https://doi.org/10.1007/8904_2017_48
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