Leigh syndrome, French Canadian type, also known as congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, is a rare mitochondrial disorder which is characterized by regular metabolic acidosis, hypotonia, developmental delays and facial dysmorphy.[1][2] It's associated with mutations in a gene in chromosome 2. Approximately 100 cases of this syndrome have been reported in medical literature.[3]
Presentation
editPeople with the disorder often don't show any symptoms at birth, but instead start showing them by early infancy; babies with this condition usually start losing basic motor skills (such as walking, moving their head, etc.), they may also show intellectual disabilities, facial dysmorphy, irritability, changes in behavior, epilepsy, low blood sugar, vomiting, diarrhea, and constant fatigue.
The brain and cognitive/intellectual symptoms are mainly caused by a deterioration in the myelin sheath that protect the cells in the brainstem and/or midbrain.
The general health symptoms are mainly caused by accumulation of toxic substances in the blood. These symptoms generally affect vision, the heart, and breathing difficulties.[4]
Causes
editThis disorder is caused by an autosomal recessive mutation in the LRPPRC gene in chromosome 2p16. To be more specific, it is caused by a base pair substitution of 'C to T" 1119 base pairs into this gene. This transition results in a missense mutation that turns a highly conserved alanine into valine.[5]
Etiology
editThis condition is surprisingly common among Canadians of French descent in Saguenay-Lac-Saint-Jean, Quebec, Canada.[6] In this area, this disorder occurs in 1 out of every 2,178 live births.[7]
This disorder was first discovered in August 1993, when F Merante et al. described 34 children in the Saguenay-Lac-Saint-Jean area with a peculiar, never seen before variant of Leigh syndrome.[8]
References
edit- ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Congenital lactic acidosis Saguenay Lac Saint Jean type Leigh syndrome French Canadian type". www.orpha.net. Retrieved 2022-05-19.
{{cite web}}: CS1 maint: numeric names: authors list (link) - ^ "Leigh syndrome, French Canadian type - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-05-19.
- ^ "OMIM Entry - # 220111 - MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 5; MC4DN5". omim.org. Retrieved 2022-05-20.
- ^ "Myriad Women's Health". Myriad Women's Health. Retrieved 2022-05-20.
- ^ Cooper, Marcus P.; Qu, Lishu; Rohas, Lindsay M.; Lin, Jiandie; Yang, Wenli; Erdjument-Bromage, Hediye; Tempst, Paul; Spiegelman, Bruce M. (2006-11-01). "Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1α/LRP130 complex". Genes & Development. 20 (21): 2996–3009. doi:10.1101/gad.1483906. ISSN 0890-9369. PMC 1620022. PMID 17050673.
- ^ "Leigh Syndrome, French Canadian Type: Genetics and More - 23andMe". www.23andme.com. Retrieved 2022-05-20.
- ^ Lee, N.; Daly, M. J.; Delmonte, T.; Lander, E. S.; Xu, F.; Hudson, T. J.; Mitchell, G. A.; Morin, C. C.; Robinson, B. H.; Rioux, J. D. (February 2001). "A genomewide linkage-disequilibrium scan localizes the Saguenay-Lac-Saint-Jean cytochrome oxidase deficiency to 2p16". American Journal of Human Genetics. 68 (2): 397–409. doi:10.1086/318197. ISSN 0002-9297. PMC 1235273. PMID 11156535.
- ^ Merante, F.; Petrova-Benedict, R.; MacKay, N.; Mitchell, G.; Lambert, M.; Morin, C.; De Braekeleer, M.; Laframboise, R.; Gagné, R.; Robinson, B. H. (August 1993). "A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec". American Journal of Human Genetics. 53 (2): 481–487. ISSN 0002-9297. PMC 1682348. PMID 8392290.