Periodic Paralysis in a Child With Thermosensitive Mitochondrial Trifunctional Protein Deficiency.
HADHA gene
LCHAD
MTP
bulbar involvement
long‐chain 3‐hydroxyacyl‐CoA dehydrogenase
mitochondrial trifunctional protein deficiency
periodic paralysis
thermosensitivity
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
03 Oct 2024
03 Oct 2024
Historique:
revised:
15
09
2024
received:
02
06
2024
accepted:
20
09
2024
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
3
10
2024
Statut:
aheadofprint
Résumé
Mitochondrial trifunctional protein (MTP) deficiency is a fatty acid oxidation disorder associated with a spectrum of phenotypes. Patients with high residual enzyme activity tend to have milder phenotypes, and recently, fever-induced episodic myopathy was reported in association with a thermosensitive form of MTP deficiency. We report a 10-year-old male with recurrent episodes of acute flaccid paralysis involving upper and lower extremities in association with bulbar muscle weakness in the context of febrile illness, a phenotype reminiscent of recurrent periodic paralysis. The episodes started at the age of 3 years and have always been followed by full recovery within 1-2 weeks with no residual weakness. Whole exome sequencing revealed a homozygous c.2132C > T, p.(Pro711Leu) variant in HADHA. The variant leads to mildly reduced long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain ketoacyl-CoA thiolase (LCKAT) enzyme activities and reduced MTP protein expression in patient's fibroblasts when cultured at 37°C. Enzyme activities and MTP protein expression diminished when fibroblasts were cultured at 40°C. This is the first published report of confirmed recurrent periodic paralysis as a manifestation of a thermosensitive form of MTP deficiency, and it calls for this condition to be considered when evaluating patients with recurrent periodic paralysis given therapeutic implications.
Identifiants
pubmed: 39360520
doi: 10.1002/ajmg.a.63900
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63900Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
Carpenter, K., R. J. Pollitt, and B. Middleton. 1992. “Human Liver Long‐Chain 3‐Hydroxyacyl‐Coenzyme a Dehydrogenase is a Multifunctional Membrane‐Bound Beta‐Oxidation Enzyme of Mitochondria.” Biochemical and Biophysical Research Communications 183, no. 2: 443–448. https://doi.org/10.1016/0006‐291X(92)90501‐B.
Den Boer, M. E. J., R. J. A. Wanders, A. A. M. Morris, L. Ijlst, H. S. A. Heymans, and F. A. Wijburg. 2002. “Long‐Chain 3‐Hydroxyacyl‐CoA Dehydrogenase Deficiency: Clinical Presentation and Follow‐Up of 50 Patients.” Pediatrics 109, no. 1: 99–104. https://doi.org/10.1542/peds.109.1.99.
Diebold, I., U. Schön, R. Horvath, et al. 2019. “HADHA and HADHB Gene Associated Phenotypes—Identification of Rare Variants in a Patient Cohort by Next Generation Sequencing.” Molecular and Cellular Probes 44: 14–20. https://doi.org/10.1016/j.mcp.2019.01.003.
Diekman, E. F., W. L. Van Der Pol, R. A. J. Nievelstein, S. M. Houten, F. A. Wijburg, and G. Visser. 2014. “Muscle MRI in Patients With Long‐Chain Fatty Acid Oxidation Disorders.” Journal of Inherited Metabolic Disease 37, no. 3: 405–413. https://doi.org/10.1007/s10545‐013‐9666‐3.
Fletcher, A. L., M. E. Pennesi, C. O. Harding, R. G. Weleber, and M. B. Gillingham. 2012. “Observations Regarding Retinopathy in Mitochondrial Trifunctional Protein Deficiencies.” Molecular Genetics and Metabolism 106, no. 1: 18–24. https://doi.org/10.1016/j.ymgme.2012.02.015.
Jank, J. M., E. M. Maier, D. D. Reib, et al. 2014. “The Domain‐Specific and Temperature‐Dependent Protein Misfolding Phenotype of Variant Medium‐Chain Acyl‐CoA Dehydrogenase.” PLoS One 9, no. 4: e93852. https://doi.org/10.1371/journal.pone.0093852.
Kamijo, T., T. Aoyama, J. I. Miyazaki, and T. Hashimoto. 1993. “Molecular Cloning of the cDNAs for the Subunits of Rat Mitochondrial Fatty Acid β‐Oxidation Multienzyme Complex. Structural and Functional Relationships to Other Mitochondrial and Peroxisomal β‐Oxidation Enzymes.” Journal of Biological Chemistry 268, no. 35: 26452–26460. https://doi.org/10.1016/s0021‐9258(19)74336‐1.
Olpin, S. E. 2013. “Pathophysiology of Fatty Acid Oxidation Disorders and Resultant Phenotypic Variability.” Journal of Inherited Metabolic Disease 36: 645–658. https://doi.org/10.1007/s10545‐013‐9611‐5.
Olpin, S. E., N. J. Manning, R. J. Pollitt, and S. Clarke. 1997. “Improved Detection of Long‐Chain Fatty Acid Oxidation Defects in Intact Cells Using [9,10‐3H]Oleic Acid.” Journal of Inherited Metabolic Disease 20, no. 3: 415–419. https://doi.org/10.1023/A:1005358802096.
Remiche, G., P. Baudin, C. Buon, et al. 2017. “Trifunctional Protein Beta Subunit (HADHB) Mutations Associated With Periodic Paralysis Phenotype.” Neuromuscular Disorders 27: S164. https://doi.org/10.1016/j.nmd.2017.06.258.
Schwantje, M., M. S. Ebberink, M. Doolaard, et al. 2022. “Thermo‐Sensitive Mitochondrial Trifunctional Protein Deficiency Presenting With Episodic Myopathy.” Journal of Inherited Metabolic Disease 45, no. 4: 819–831. https://doi.org/10.1002/jimd.12503.
Schwantje, M., S. A. Fuchs, L. de Boer, et al. 2022. “Genetic, Biochemical, and Clinical Spectrum of Patients With Mitochondrial Trifunctional Protein Deficiency Identified After the Introduction of Newborn Screening in The Netherlands.” Journal of Inherited Metabolic Disease 45, no. 4: 804–818. https://doi.org/10.1002/jimd.12502.
Spiekerkoetter, U., B. Sun, Z. Khuchua, M. J. Bennett, and A. W. Strauss. 2003. “Molecular and Phenotypic Heterogeneity in Mitochondrial Trifunctional Protein Deficiency Due to Beta‐Subunit Mutations.” Human Mutation 21, no. 6: 598–607. https://doi.org/10.1002/HUMU.10211.
Uzun, Ö. Ü., B. Çavdarlı, and S. Karalök. 2021. “Mitochondrial Trifunctional Protein Deficiency as a Polyneuropathy Etiology in Childhood.” Turkish Journal of Pediatrics 63, no. 6: 1097–1102. https://doi.org/10.24953/turkjped.2021.06.020.
van Hove, J. L. K., S. G. Kahler, M. D. Feezor, et al. 2000. “Acylcarnitines in Plasma and Blood Spots of Patients With Long‐Chain 3‐Hydroxyacyl‐Coenzyme A Dehydrogenase Deficiency.” Journal of Inherited Metabolic Disease 23, no. 6: 571–582. https://doi.org/10.1023/A:1005673828469.
Venance, S. L., S. C. Cannon, D. Fialho, et al. 2006. “The Primary Periodic Paralyses: Diagnosis, Pathogenesis and Treatment.” Brain 129, no. 1: 8–17.
Xia, C., Z. Fu, K. P. Battaile, and J. J. P. Kim. 2019. “Crystal Structure of Human Mitochondrial Trifunctional Protein, a Fatty Acid β‐Oxidation Metabolon.” Proceedings of the National Academy of Sciences of the United States of America 116, no. 13: 6069–6074. https://doi.org/10.1073/pnas.1816317116.