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Mutations in CoA Synthase as a cause of NBIA

Posted by & filed under Part 28: NEUROGENETICS, _.

Dusi et al (AJHG, 94, 11-22) report mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation (NBIA). This gene is particularly interesting, as another member of the CoA biosynthetic pathway, PANK2, also causes NBIA. It is not clear why a gene with such seemingly ubiquitous function should cause such specific neurologic […]



3-hydroxy-isobutyryl-CoA hydrolase deficiency causing deficiency of multiple mitochondrial respiratory chain enzymes and of the pyruvate dehydrogenase complex

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

Ferdinandusse S et al. HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase. Orphanet J Rare Dis. 2013 Dec 4;8:188.   Ferdinandusse et al describe two new patients (for a total of four patients described on the literature) with 3-hydroxy-isobutyryl-CoA hydrolase deficiency, a disorder of valine […]



A novel mechanism for mitochondrial toxicity of valproic acid

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

Luís PB et al (2013) Valproyl-CoA inhibits the activity of ATP- and GTP-dependent succinate:CoA ligases. J Inherit Metab Dis. 2013 Oct 24. [Epub ahead of print]   Luis et al propose a new mechanism for valproic acid-induced mitochondrial dysfunction, particularly in patients with deficiencies of the mtDNA replication machinery. Succinate:CoA ligase (SUCL), also known as […]



Duplications of 22q11.2 protect against schizophrenia?

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Rees et al analyzed a cohort of 47,005 individuals for large duplications (1.5-3.0Mb) at 22q11.2 -the reciprocal of the well-known, risk-inducing deletion of this locus. These duplications were found to be substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). The authors suggest that duplications of the genomic […]



toxicity of 3-hydroxylated fatty acids

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Cardiomyopathy is a well known complication of LCHAD deficiency and Mitochondrial Trifunctional protein (MTP) deficiency. Tonin et al (in J Bioenerg Biomech 2013 Feb;45(1-2):47-57) offer evidence that several 3-hydroxylated fatty acids that accumulate in MTP and LCHAD deficiencies act as uncouplers of oxidative phosphorylation.This could potentially interfere with cardiac energy homeostasis. It would be interesting to better understand […]



Standardizing clinical info for research and diagnosis

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This article is describing an open source software for collecting and analyzing phenotypic information for patients with genetic disorders (PhenoTips). The PhenoTips’ user interface resembles clinician workflows to facilitate recording observations made during the patient encounter. It allows for efficient data entry, standardization of collected patient phenotypes, and sharing of anonymized patient phenotype data thus rendering it very useful […]



Glycerol phenylbutyrate and hepatic encephalopathy

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Our genetics service has been consulted several times recently about whether or not nitrogen scavenging agents typically used in urea cycle disorders would be useful in individuals with hepatic encephalopathy (HE) due to liver failure, i.e. from cirrhosis. Our a priori reasoning was that these scavenging agents may not be as effective in HE because they rely on alternative […]



S-adenosylmethionine and S-adenosyl homocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation

Posted by & filed under Part 17: VITAMINS, Part 28: NEUROGENETICS, _.

Hagebeuk EEO et al. S-adenosylmethionine and S-adenosyl homocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation. J Inherited Metab Dis (2013) 36:967-972   Rett syndrome, a devastating disorder characterised by neuroregression after an initial period of normalcy, is caused by mutations in the MECP2 gene encoding the methyl […]



Vitamin D and cardiomyopathy in Fabry disease

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, _.

Drechsler C et al. Potential role of Vitamin D deficiency on Fabry cardiomyopathy. J Inherit Metab Dis. 2013 Oct 19. [Epub ahead of print] Vitamin D has been implicated in cardiac metabolism, although its exact role is still unclear. As Fabry patients are at risk for vitamin D deficiency due to a combination of sunlight […]



Mitochondrial Cristae and Supercomplexes

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In a very well thought out group of experiments, Cogliati et al. demonstrated the effect that disturbed mitochondrial cristae shape has on respiratory chain supercomplexes (Cell, 155, (2013)160-171). This supercomplex effect has implications for cell growth, apoptosis, and respiratory efficiency. These studies suggest potentially interesting pathophysiological mechanisms for other disorders affecting cristae organization, such as 3-methyglutaconic […]