Posts Categorized: Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION



FAOD and oxidative stress

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Mice models of VLCAD develop oxidative stress in the liver upon fasting, suggesting reactive oxygen species are important culprits in the hepatopathy of affected patients (Tucci et al, 2010, FEBS J 277:4699-708). Increased oxidative stress was also seen when over-expressing a mutant SCAD in cultured cells (Schmidt et al, 2010, Mol Genet Metab 100:155-62), while […]



IDH1 mutation in gliomas

Posted by & filed under Part 04: CANCER, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Certain gliomas have somatic mutation in cytosolic isocitrate dehydrogenase 1. Dang et al. have shown that these mutations confer the enzyme the new ability to transform alpha-ketoglutarate in 2-hydroxyglutarate. This metabolite might be oncogenic, although this is not proven yet. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462:739-744 […]



Succinate dehydrogenase and leukoencephalopathy

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 28: NEUROGENETICS, _.

A gene encoding a protein essential for the assembly of succinate dehydrogenase has been implicated in an infantile leukoencephalopathy. Nat Genet. 2009 May 24. [Epub ahead of print] SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Ghezzi D et al. Click this link to see the most recent online […]



Mitochondrial carrier and sideroblastic anemia

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 13: PORPHYRINS, Part 19: BLOOD, _.

Nat Genet. 2009 Jun;41(6):651-3. Epub 2009 May 3. Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia. Guernsey DL et al. These investigators form Nova Scotia describe a new form of sideroblastic anemia caused by a mutation in a mitochondrial carrier. The gene was identified by positional cloning. Click this […]



New cause of CoQ10 deficiency

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, _.

Am J Hum Genet. 2009 May;84(5):558-66. Epub 2009 Apr 16. A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease. Duncan AJ et al. This group from the UK describes a new form of coQ10 deficiency, a potentially treatable condition. Click this link to see the […]



New Krebs cycle defect

Posted by & filed under New IEM, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Nat Genet. 2008 Oct;40(10):1230-4. Epub 2008 Sep 21. Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle. Hartong DT, Dange M, McGee TL, Berson EL, Dryja TP, Colman RF. We still have things to learn about the Krebs cycle…. Indeed, by studying families with Retinitis Pigmentosa, Hartong and colleagues identified […]



Another gene involved in ubiquinone deficiency

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Am J Hum Genet. 2008 Mar;82(3):623-30. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A. Investigators rom Paris have studied patients with CoQ10 deficiency from three families […]



Reversion of white matter changes with treatment of HMG-CoA lyase deficiency.

Posted by & filed under Part 09: ORGANIC ACIDS, Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Treatment.

Pediatr Neurol. 2007 Jul;37(1):47-50. 3-Hydroxy-3-methylglutaryl coenzyme a lyase deficiency with reversible white matter changes after treatment. Zafeiriou DI, Vargiami E, Mayapetek E, Augoustidou-Savvopoulou P, Mitchell GA.   In this paper, the authors describe a patient with HMG-CoA Lyase deficiency. He initially presented at 8 months with seizures during a gastroenteritis; he had hepatomegaly and elevated […]



Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, _.

A group led by Orly Elpeleg has identified a gene associated with pontocerebellar hypoplasia, a heterogenous group of conditions. Deleterious Mutation in the Mitochondrial ArginylTransfer RNA Synthetase Gene Is Associated with Pontocerebellar Hypoplasia Simon Edvardson, Avraham Shaag, Olga Kolesnikova, John Moshe Gomori, Ivan Tarassov, Tom Einbinder, Ann Saada, and Orly Elpeleg The American Journal of […]



A lethal defect of mitochondrial and peroxisomal fission

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 15: PEROXISOMES.

N Engl J Med. 2007 Apr 26;356(17):1707-9. A lethal defect of mitochondrial and peroxisomal fission. Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV. girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia. Biochemical analyses revealed lactic acidosis and an increase in very-long-chain fatty acids. Because the peroxisomes and mitochondria […]