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Mitochondrial Encephalopathy and Transient 3-Methylglutaconic Aciduria in ECHS1 Deficiency: Long-Term Follow-Up

  • Irene C. Huffnagel
  • Egbert J. W. Redeker
  • Liesbeth Reneman
  • Frédéric M. Vaz
  • Sacha Ferdinandusse
  • Bwee Tien Poll-The
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

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.

Keywords

3-Methylglutaconic aciduria Developmental disorders ECHS1 Mitochondrial disorders MRI Whole exome sequencing 

Notes

Acknowledgements

We thank Dr. Alberto Burlina (University of Padua, Italy) for providing a urine sample from a previously reported ECHS1 case for comparison.

References

  1. Al Mutairi F, Shamseldin HE, Alfadhel M, Rodenburg RJ, Alkuraya FS (2017) A lethal neonatal phenotype of mitochondrial short-chain enoyl-CoA hydratase-1 deficiency. Clin Genet 91:629–633CrossRefPubMedGoogle Scholar
  2. Bedoyan JK, Yang SP, Ferdinandusse S et al (2017) Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency. Mol Genet Metab 120:342–349CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ferdinandusse S, Friederich MW, Burlina A et al (2015) Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet J Rare Dis 10:79CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ganetzky RD, Bloom K, Ahrens-Nicklas R et al (2016) ECHS1 deficiency as a cause of severe neonatal lactic acidosis. JIMD Rep 30:33–37CrossRefPubMedPubMedCentralGoogle Scholar
  5. Haack TB, Jackson CB, Murayama K et al (2015) Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement. Ann Clin Transl Neurol 2:492–509CrossRefPubMedPubMedCentralGoogle Scholar
  6. Mahajan A, Constantinou J, Sidiropoulos C (2017) ECHS1 deficiency-associated paroxysmal exercise-induced dyskinesias: case presentation and initial benefit of intervention. J Neurol 264:185–187CrossRefPubMedGoogle Scholar
  7. Nair P, Hamzeh AR, Mohamed M, Malik EM, Al-Ali MT, Bastaki F (2016) Novel ECHS1 mutation in an Emirati neonate with severe metabolic acidosis. Metab Brain Dis 31:1189–1192CrossRefPubMedGoogle Scholar
  8. Olgiati S, Skorvanek M, Quadri M et al (2016) Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency. Mov Disord 31(7):1041–1048CrossRefPubMedGoogle Scholar
  9. Peters H, Buck N, Wanders R et al (2014) ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism. Brain 137:2903–2908CrossRefPubMedGoogle Scholar
  10. Sakai C, Yamaguchi S, Sasaki M, Miyamoto Y, Matsushima Y, Goto Y (2015) ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome. Hum Mutat 36:232–239CrossRefPubMedGoogle Scholar
  11. Tetreault M, Fahiminiya S, Antonicka H et al (2015) Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome. Hum Genet 134:981–991CrossRefPubMedGoogle Scholar
  12. Wanders RJ, Duran M, Loupatty FJ (2012) Enzymology of the branched-chain amino acid oxidation disorders: the valine pathway. J Inherit Metab Dis 35:5–12CrossRefPubMedGoogle Scholar
  13. Wortmann SB, Duran M, Anikster Y et al (2013) Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. J Inherit Metab Dis 36:923–928CrossRefPubMedGoogle Scholar
  14. Yamada K, Aiba K, Kitaura Y et al (2015) Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion. J Med Genet 52:691–698CrossRefPubMedGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2017

Authors and Affiliations

  • Irene C. Huffnagel
    • 1
  • Egbert J. W. Redeker
    • 2
  • Liesbeth Reneman
    • 3
  • Frédéric M. Vaz
    • 4
  • Sacha Ferdinandusse
    • 4
  • Bwee Tien Poll-The
    • 1
  1. 1.Department of Paediatric NeurologyEmma Children’s Hospital, Academic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Clinical GeneticsAcademic Medical CenterAmsterdamThe Netherlands
  3. 3.Department of RadiologyAcademic Medical CenterAmsterdamThe Netherlands
  4. 4.Laboratory Genetic Metabolic DiseasesAcademic Medical CenterAmsterdamThe Netherlands

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