LYRM7-associated mitochondrial complex III deficiency with non-cavitating leukoencephalopathy and stroke-like episodes.

Autor: Alfattal R; Department of Pediatrics, Al-Amiri Hospital, Ministry of Health, Kuwait., Alfarhan M; Department of Pediatrics, Health Sciences Centre, Faculty of Medicine, Kuwait University, Safat, Kuwait., Algaith AM; University of Szeged, Faculty of Medicine, Hungary., Albash B; Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Elshafie RM; Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Alshammari A; Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Alahmad A; Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait., Dashti F; Department of Radiology, Ibn Sina Hospital, Ministry of Health, Safat, Kuwait., Alsafi R; Department of Pediatrics, Adan Hospital, Ministry of Health, Hadiya, Kuwait., Alsharhan H; Department of Pediatrics, Health Sciences Centre, Faculty of Medicine, Kuwait University, Safat, Kuwait.; Kuwait Medical Genetics Center, Ministry of Health, Sulaibikhat, Kuwait.; Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al-Nasser, Kuwait.; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2023 May; Vol. 191 (5), pp. 1401-1411. Date of Electronic Publication: 2023 Feb 09.
DOI: 10.1002/ajmg.a.63143
Abstrakt: Defects of respiratory chain complex III (CIII) result in characteristic but rare mitochondrial disorders associated with distinct neuroradiological findings. The underlying molecular defects affecting mitochondrial CIII assembly factors are few and yet to be identified. LYRM7 assembly factor is required for proper CIII assembly where it acts as a chaperone for the Rieske iron-sulfur (UQCRFS1) protein in the mitochondrial matrix and stabilizing it. We present here the seventeenth individual with LYRM7-associated mitochondrial leukoencephalopathy harboring a previously reported rare pathogenic homozygous LYRM 7 variant, c.2T>C, (p.Met1?). Like previously reported individuals, our 5-year-old male proband presented with recurrent metabolic and lactic acidosis, encephalopathy, and fatigue. Further, he has additional, previously unreported features, including an acute stroke like episode with bilateral central blindness and optic neuropathy, recurrent hyperglycemia and hypertension associated with metabolic crisis. However, he has no signs of psychomotor regression. He has been stable clinically with residual left-sided reduced visual acuity and amblyopia, and no more metabolic crises for 2-year-period while on the mitochondrial cocktail. Although the reported brain MRI findings in other affected individuals are homogenous, it is slightly different in our index, revealing evidence of bilateral almost symmetric multifocal periventricular T2 hyperintensities with hyperintensities of the optic nerves, optic chiasm, and corona radiata but with no cavitation or cystic changes. This report describes new clinical and radiological findings of LYRM7-associated disease. The report also summarizes the clinical and molecular data of previously reported individuals describing the full phenotypic spectrum.
(© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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