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Journal of Inherited Metabolic Disease

, Volume 40, Issue 5, pp 745–747 | Cite as

Unique presentation of cutis laxa with Leigh-like syndrome due to ECHS1 deficiency

  • S. Balasubramaniam
  • L. G. Riley
  • D. Bratkovic
  • D. Ketteridge
  • N. Manton
  • M. J. Cowley
  • V. Gayevskiy
  • T. Roscioli
  • M. Mohamed
  • T. Gardeitchik
  • E. Morava
  • J. Christodoulou
Images in Metabolic Medicine

Abstract

Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)–congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.

Keywords

Transaldolase Cutis Laxa Respiratory Chain Enzyme Activity Compound Heterozygous Variant Mitochondrial Matrix Enzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This research was supported by a New South Wales Office of Health and Medical Research Council Sydney Genomics Collaborative grant (JC) and NHMRC project grant 1026891 (JC). We are grateful to the Crane and Perkins families for their generous financial support. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

The authors wish to acknowledge the family and The Netherlands Organisation for Scientific Research (NWO project 017.008.052 to M.M.), and the Dutch Stofwisselkracht Foundation (TG) for their collaboration.

Compliance with ethical standards

Conflict of interest

S. Balasubramaniam, L. G. Riley, D. Bratkovic, D. Ketteridge, N. Manton, M. J. Cowley, V. Gayevskiy, T. Roscioli, M. Mohamed and T. Gardeitchik declare they have no conflict of interest. E. Morava is the Editor-in-Chief of the Journal of Inherited Metabolic Disease. J. Christodoulou is a communicating editor of the Journal of Inherited Metabolic Disease.

Funding

This research was supported by a New South Wales Office of Health and Medical Research Council Sydney Genomics Collaborative grant (JC) and NHMRC project grant 1026891 (JC). We are grateful to the Crane and Perkins families for their generous financial support. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

References

  1. Ferdinandusse S, Friederich MW, Burlina A et al (2015) Clinical and biochemical characterization of four patients with mutations in ECHS1. Orphanet Journal of Rare Diseases 10:79Google Scholar
  2. Mohamed M, Kouwenberg D, Gardeitchik T et al (2011) Metabolic cutis laxa syndromes. J Inherit Metab Dis 34:907–916Google Scholar
  3. Tetreault M, Fahiminiya S, Antonicka H et al (2015) Whole‑exome sequencing identifies novel ECHS1 mutations in Leigh syndrome. Hum Genet 134:981–991Google Scholar

Copyright information

© SSIEM 2017

Authors and Affiliations

  • S. Balasubramaniam
    • 1
    • 2
    • 3
    • 4
  • L. G. Riley
    • 4
    • 5
  • D. Bratkovic
    • 6
  • D. Ketteridge
    • 6
  • N. Manton
    • 7
  • M. J. Cowley
    • 8
  • V. Gayevskiy
    • 8
  • T. Roscioli
    • 8
    • 9
    • 10
  • M. Mohamed
    • 11
    • 12
  • T. Gardeitchik
    • 11
    • 12
  • E. Morava
    • 11
    • 13
  • J. Christodoulou
    • 1
    • 3
    • 4
    • 5
    • 14
    • 15
  1. 1.Western Sydney Genetics ProgramThe Children’s Hospital at WestmeadSydneyAustralia
  2. 2.Genetic Metabolic Disorders Service, Western Sydney Genetics ProgramThe Children’s Hospital at WestmeadWestmeadAustralia
  3. 3.Discipline of Genetic Medicine, Sydney Medical SchoolUniversity of SydneySydneyAustralia
  4. 4.Discipline of Paediatrics & Child Health, Sydney Medical SchoolUniversity of SydneySydneyAustralia
  5. 5.Genetic Metabolic Disorders Research UnitThe Children’s Hospital at Westmead, KRISydneyAustralia
  6. 6.Metabolic Unit, SA PathologyWomen’s and Children’s HospitalNorth AdelaideAustralia
  7. 7.Department of Surgical Pathology, SA PathologyWomen’s and Children’s HospitalNorth AdelaideAustralia
  8. 8.Kinghorn Centre for Clinical GenomicsGarvan Institute of Medical ResearchSydneyAustralia
  9. 9.St Vincent’s Clinical SchoolUniversity of New South WalesSydneyAustralia
  10. 10.Department of Medical GeneticsSydney Children’s HospitalRandwickAustralia
  11. 11.Institute for Genetic and Metabolic DiseaseRadboud University Medical Centre NijmegenNijmegenThe Netherlands
  12. 12.Department of PediatricsRadboud University Medical Centre NijmegenNijmegenThe Netherlands
  13. 13.Hayward Genetics CenterTulane University Medical CenterNew OrleansUSA
  14. 14.Murdoch Children’s Research Institute and Victorian Clinical Genetics ServicesRoyal Children’s HospitalMelbourneAustralia
  15. 15.Department of PaediatricsUniversity of MelbourneMelbourneAustralia

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