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Thermo-sensitive mi...
Thermo-sensitive mitochondrial trifunctional protein deficiency presenting with episodic myopathy
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Schwantje, M. (author)
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Ebberink, M. S. (author)
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Doolaard, M. (author)
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Ruiter, J. P. N. (author)
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Fuchs, S. A. (author)
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- Darin, Niklas, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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- Oldfors Hedberg, Carola, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Regal, L. (author)
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Kaat, L. D. (author)
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Huidekoper, H. H. (author)
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Olpin, S. (author)
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Cole, D. (author)
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Moat, S. J. (author)
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Visser, G. (author)
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Ferdinandusse, S. (author)
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(creator_code:org_t)
- 2022-05-05
- 2022
- English.
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In: Journal of Inherited Metabolic Disease. - : Wiley. - 0141-8955 .- 1573-2665. ; 45:4, s. 819-831
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- long-chain fatty acid oxidation disorders
- long-chain ketoacyl-CoA
- thiolase deficiency
- mitochondrial trifunctional protein complex
- mitochondrial trifunctional protein deficiency
- myopathy
- thermo-sensitivity
- fatty-acid oxidation
- beta-oxidation
- defects
- pathophysiology
- dehydrogenase
- disorders
- mutations
- enzyme
- Endocrinology & Metabolism
- Genetics & Heredity
- Research & Experimental
- Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Schwantje, M.
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Ebberink, M. S.
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Doolaard, M.
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Ruiter, J. P. N.
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Fuchs, S. A.
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Darin, Niklas, 1 ...
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show more...
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Oldfors Hedberg, ...
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Regal, L.
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Kaat, L. D.
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Huidekoper, H. H ...
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Olpin, S.
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Cole, D.
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Moat, S. J.
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Visser, G.
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Ferdinandusse, S ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Pediatrics
- Articles in the publication
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Journal of Inher ...
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University of Gothenburg