3,806 research outputs found
CARNITINE-ACYLCARNITINE TRANSLOCASE DEFICIENCY (CACT) REFERENCES (SOLUTE CARRIER FAMILY 25 (CARNITINE/ACYLCARNITINE TRANSLOCASE), MEMBER 20;
No full textacylcarnitine translocase gene in a Saudi patient, ” Clin Genet. 2003 Aug; 64(2): 163-5. 2. al Aqeel AI, Rashed MS, Wanders RJ. “Carnitine-acylcarnitine translocase deficiency is a treatabl
Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency due to a Novel Missense Mutation
No full textDeficiency of carnitine/acylcarnitine translocase (CACT) is an autosomal recessive disorder of the carnitine cycle resulting in the inability to transfer fatty acids across the inner mitochondrial membrane. Only a limited number of affected patients have been reported and the effect of therapy on this condition is still not well defined. Here, we report a new patient with this disorder and follow the response to therapy. Our patient was the product of a consanguineous marriage. He presented shortly after birth with cardiac myopathy and arrhythmia coupled with severe non-ketotic hypoglycemia. Initial metabolic studies indicated severe non-ketotic C6-C10 dicarboxylic aciduria, plasma carnitine deficiency, and a characteristic elevation of plasma C:16:0, C18:1, and C18:2 acylcarnitine species. Enzyme assay confirmed deficiency of CACT activity. Molecular studies indicated that this child was homozygous, and both parents heterozygous, for a single bp change converting glutamine 238 to arginine (Q238R). Therapy with a formula providing most of the fat via medium chain triglycerides (MCT) and carnitine supplementation reduced the concentration of long-chain acylcarnitines and reversed cardiac symptoms and the hypoglycemia. These results suggest that carnitine and MCT may be effective in treating this defect of long-chain fatty acid oxidatio
Ablation of Steroid Receptor Coactivator-3 Resembles the Human CACT Metabolic Myopathy
No full textSummaryOxidation of lipid substrates is essential for survival in fasting and other catabolic conditions, sparing glucose for the brain and other glucose-dependent tissues. Here we show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. Genetic deficiency of CACT in humans is accompanied by a constellation of metabolic and toxicity phenotypes including hypoketonemia, hypoglycemia, hyperammonemia, and impaired neurologic, cardiac and skeletal muscle performance, each of which is apparent in mice lacking SRC-3 expression. Consistent with human cases of CACT deficiency, dietary rescue with short chain fatty acids drastically attenuates the clinical hallmarks of the disease in mice devoid of SRC-3. Collectively, our results position SRC-3 as a key regulator of β-oxidation. Moreover, these findings allow us to consider platform coactivators such as the SRCs as potential contributors to syndromes such as CACT deficiency, previously considered as monogenic
A novel homozygous missense SLC25A20 mutation in three CACT-deficient patients : clinical and autopsy data
Get PDFCarnitine-acylcarnitine translocase (CACT) deficiency is a fatty acid ß-oxidation disorder of the carnitine shuttle in mitochondria, with a high mortality rate in childhood. We evaluated three patients, including two siblings, with neonatal-onset CACT deficiency and revealed identical homozygous missense mutations of p.Arg275Gln within the SLC25A20 gene. One patient died from hypoglycemia and arrhythmia at 26 months; his pathological autopsy revealed increased and enlarged mitochondria in the heart but not in the liver.論
Dried blood spot acylcarnitines from selective screening for detection of Carnitine-acylcarnitine Translocase (CACT) deficiency and Carnitine palmitoyl transferase 2 (CPT2) deficiency by electrospray tandem mass spectrometry.
No full textThe dataset was generated from analysis of acylcarnitines in the 17,121 dried blood spots using tandem mass spectrometry operated with electrospray in positive ion mode. Precursor ion scan of m/z 85 was used for all acylcarnitines and quantification of each analyte was obtained using the signal intensity ratio of the compound to its internal standard. The acylcarnitines analyzed included C0, C2, C3, C3DC, C4, C5, C5:1, C5DC, C5OH, C6, C8, C10, C12, C14, C16, C18, C18:1, C16OH, C18OH and C18:1OH. The data was analyzed using Neolynx V4.0 software. The data analysis was obtained from measurement of acylcarnitines from symptomatic Malaysian patients less than fifty years old who exhibiting symptoms suggestive of inborn errors of metabolism, but had normal acylcarnitine profile. These data on the acylcarnitines derived from the dried blood spot (DBS) and their respective calculated acylcarnitine ratios has been used in patients with clinically suspected long chain fatty acid oxidation disorders, Carnitine-acylcarnitine Translocase (CACT) deficiency and carnitine palmitoyl transferase 2 (CPT2) deficiency. In our patient population, the 99th percentile was used as the cut-offs to detect the disease. The individual acylcarnitines and the relevant acylcarnitine ratios and spectrums of normal and positive patients with Carnitine-acylcarnitine Translocase (CACT) deficiency and carnitine palmitoyl transferase 2 (CPT2) deficiency generated from analysis by tandem mass spectrometry are provided as attached files.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Dried blood spot acylcarnitines from selective screening for detection of Carnitine-acylcarnitine Translocase (CACT) deficiency and Carnitine palmitoyl transferase 2 (CPT2) deficiency by electrospray tandem mass spectrometry.
No full textThe dataset was generated from analysis of acylcarnitines in the 17,121 dried blood spots using tandem mass spectrometry operated with electrospray in positive ion mode. Precursor ion scan of m/z 85 was used for all acylcarnitines and quantification of each analyte was obtained using the signal intensity ratio of the compound to its internal standard. The acylcarnitines analyzed included C0, C2, C3, C3DC, C4, C5, C5:1, C5DC, C5OH, C6, C8, C10, C12, C14, C16, C18, C18:1, C16OH, C18OH and C18:1OH. The data was analyzed using Neolynx V4.0 software. The data analysis was obtained from measurement of acylcarnitines from symptomatic Malaysian patients less than fifty years old who exhibiting symptoms suggestive of inborn errors of metabolism, but had normal acylcarnitine profile. These data on the acylcarnitines derived from the dried blood spot (DBS) and their respective calculated acylcarnitine ratios has been used in patients with clinically suspected long chain fatty acid oxidation disorders, Carnitine-acylcarnitine Translocase (CACT) deficiency and carnitine palmitoyl transferase 2 (CPT2) deficiency. In our patient population, the 99th percentile was used as the cut-offs to detect the disease. The individual acylcarnitines and the relevant acylcarnitine ratios and spectrums of normal and positive patients with Carnitine-acylcarnitine Translocase (CACT) deficiency and carnitine palmitoyl transferase 2 (CPT2) deficiency generated from analysis by tandem mass spectrometry are provided as attached files
Carnitine-acylcarnitine translocase deficiency: a case report with autopsy
Get PDFFatty acid oxidation defects are a heterogeneous group of disorders related to the mitochondrial fatty acid oxidation pathway. Carnitine acylcarnitine translocase (CACT) is an enzyme responsible for the unidirectional transport of acylcarnitine across the inner mitochondrial membrane. This enzyme plays a crucial role in the oxidation of fatty acids. The autopsy pathology of the CACT deficiency is described in only a few cases. We describe the autopsy pathology of a child with CACT deficiency dominantly in the form of microvesicular steatosis of the hepatocytes, renal proximal tubular epithelia, cardiac myocytes, and rhabdomyocytes. The diagnosis was further confirmed on whole exome sequencing with compound heterozygous variants in the exon 1 (c.82G>T, p.Gly28Cys; likely pathogenic) and exon 5 (c.535G>A, p.Asp179Asn; uncertain significance) of the SLC25A20 gene. This case elucidates the histopathology of the liver and the detailed autopsy of a case of CACT deficiency from India
"Test me and treat me" - attitudes to vitamin D deficiency and supplementation: a qualitative study
Get PDF© 2015 BMJ Open, "Test me and treat me"-attitudes to vitamin D deficiency and supplementation: a qualitative study. This manuscript version is made available under the Creative Commons Attribution Licens
Triheptanoin: A Rescue Therapy for Cardiogenic Shock in Carnitine-acylcarnitine Translocase Deficiency
No full textCarnitine-acylcarnitine translocase (CACT) deficiency is a rare long-chain fatty acid oxidation disorder (LC-FAOD) with high mortality due to cardiomyopathy or lethal arrhythmia. Triheptanoin (UX007), an investigational drug composed of synthetic medium odd-chain triglycerides, is a novel therapy in development for LC-FAOD patients. However, cases of its safe and efficacious use to reverse severe heart failure in CACT deficiency are limited. Here, we present a detailed report of an infant with CACT deficiency admitted in metabolic crisis that progressed into severe cardiogenic shock who was successfully treated by triheptanoin. The child was managed, thereafter, on triheptanoin until her death at 3 years of age from a cardiopulmonary arrest in the setting of acute respiratory illness superimposed on chronic hypercarbic respiratory failure
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
Get PDFDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
- …
