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  • Schwantje, M. (author)

Thermo-sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-05-05
  • Wiley,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/316437
  • https://gup.ub.gu.se/publication/316437URI
  • https://doi.org/10.1002/jimd.12503DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Mitochondrial trifunctional protein (MTP) is involved in long-chain fatty acid beta-oxidation (lcFAO). Deficiency of one or more of the enzyme activities as catalyzed by MTP causes generalized MTP deficiency (MTPD), long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), or long-chain ketoacyl-CoA thiolase deficiency (LCKATD). When genetic variants result in thermo-sensitive enzymes, increased body temperature (e.g. fever) can reduce enzyme activity and be a risk factor for clinical decompensation. This is the first description of five patients with a thermo-sensitive MTP deficiency. Clinical and genetic information was obtained from clinical files. Measurement of LCHAD and LCKAT activities, lcFAO-flux studies and palmitate loading tests were performed in skin fibroblasts cultured at 37 degrees C and 40 degrees C. In all patients (four MTPD, one LCKATD), disease manifested during childhood (manifestation age: 2-10 years) with myopathic symptoms triggered by fever or exercise. In four patients, signs of retinopathy or neuropathy were present. Plasma long-chain acylcarnitines were normal or slightly increased. HADHB variants were identified (at age: 6-18 years) by whole exome sequencing or gene panel analyses. At 37 degrees C, LCHAD and LCKAT activities were mildly impaired and lcFAO-fluxes were normal. Remarkably, enzyme activities and lcFAO-fluxes were markedly diminished at 40 degrees C. Preventive (dietary) measures improved symptoms for most. In conclusion, all patients with thermo-sensitive MTP deficiency had a long diagnostic trajectory and both genetic and enzymatic testing were required for diagnosis. The frequent absence of characteristic acylcarnitine abnormalities poses a risk for a diagnostic delay. Given the positive treatment effects, upfront genetic screening may be beneficial to enhance early recognition.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Ebberink, M. S. (author)
  • Doolaard, M. (author)
  • Ruiter, J. P. N. (author)
  • Fuchs, S. A. (author)
  • Darin, Niklas,1964Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xdarin (author)
  • Oldfors Hedberg, Carola,1969Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine(Swepub:gu)xnordc (author)
  • Regal, L. (author)
  • Kaat, L. D. (author)
  • Huidekoper, H. H. (author)
  • Olpin, S. (author)
  • Cole, D. (author)
  • Moat, S. J. (author)
  • Visser, G. (author)
  • Ferdinandusse, S. (author)
  • Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för pediatrik (creator_code:org_t)

Related titles

  • In:Journal of Inherited Metabolic Disease: Wiley45:4, s. 819-8310141-89551573-2665

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