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Extrapolation of Variant Phase in Mitochondrial Short-Chain Enoyl-CoA Hydratase (ECHS1) Deficiency

  • Colleen M. CarlstonEmail author
  • Sacha Ferdinandusse
  • Judith A. Hobert
  • Rong Mao
  • Nicola Longo
Research Report
Part of the JIMD Reports book series (JIMD, volume 43)

Abstract

Loss-of-function and hypomorphic ECHS1 variants are associated with mitochondrial short-chain enoyl-CoA hydratase deficiency, an inborn error of valine metabolism. We report an 8-year-old boy with developmental delay, ataxia, hemiplegia, and hearing loss with abnormalities in the basal ganglia. Biochemical studies were essentially normal except for a persistent mildly elevated CSF alanine. This patient demonstrates an intermediate phenotype between a Leigh-like, early-onset presentation and paroxysmal exercise-induced dyskinesia. Two novel ECHS1 variants (c.79T>G; p.Phe27Val and c.789_790del; p.Phe263fs) were identified via exome sequencing in the proband, and pathogenicity was confirmed by enzyme assay performed on patient fibroblasts. Neither of the ECHS1 variants detected in the child were present in the mother. However, due to nearby polymorphisms, it was possible to determine that p.Phe263fs occurred de novo on the maternal chromosome and that p.Phe27Val likely derived from the paternal chromosome. Nearby polymorphisms can help set phase of variants when only a single parent is available for testing or when an identified variant occurs de novo.

Keywords

ECHS1 Exome interpretation Mitochondrial short-chain enoyl-CoA hydratase deficiency Phase determination 

Notes

Acknowledgments

We are grateful to the family for their willingness to share this case with the medical community. We also would like to thank the members of Genomics Lab and Genetic Sequencing Lab at ARUP laboratories for performing testing on the individuals included in this study.

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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Colleen M. Carlston
    • 1
    Email author
  • Sacha Ferdinandusse
    • 2
  • Judith A. Hobert
    • 3
    • 4
  • Rong Mao
    • 3
    • 4
  • Nicola Longo
    • 3
    • 4
    • 5
  1. 1.School of MedicineUniversity of CaliforniaSan FranciscoUSA
  2. 2.Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  3. 3.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.ARUP LaboratoriesSalt Lake CityUSA
  5. 5.Department of Pediatrics/Medical GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA

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