Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare disorder that results in long-chain fatty acids being unavailable for mitochondrial beta-oxidation and ketogenesis. It can present in the neonatal period or infancy with a severe clinical form, typically with convulsions, hypothermia, encephalopathy, cardiomyopathy and liver dysfunction, or with a milder phenotype with episodes of hypoglycaemia and hyperammonaemia during intercurrent illness. Investigations show hypoketonaemia, intermittent dicarboxyluria and hypocarnitinaemia with grossly elevated acylcarnitines. Enzyme assay or DNA analysis confirms the diagnosis. The severe phenotype results in severe disability or death. The less severe phenotype can also cause significant disability secondary to hypoglycaemia and/or hyperammonaemia at presentation. We report the outcome of two siblings with CACT deficiency. The index patient presented at the age of 2 months during a respiratory illness with hypoglycaemia, hyperammonaemia and cardiorespiratory collapse. Acylcarnitine profiles showed decreased free carnitine but striking elevations of long-chain acylcarnitines. Urine organic acids showed dicarboxylic aciduria. Fatty acid oxidation studies showed reduced oleate and myristate oxidation. His acylcarnitine profile normalized after he was started on a medium-chain triglyceride (MCT) low-fat diet and carnitine supplementation. Low CACT activity on enzyme assay confirmed the diagnosis. He has resulting profound developmental delay and epilepsy. The sibling was prospectively treated with a low-fat MCT diet and carnitine supplementation. Acylcarnitine profile at birth also showed elevated long-chain acylcarnitines. Fatty acid oxidation studies confirmed the diagnosis. To date he has normal development and has not had any significant periods of hypoglycaemia or hyperammonaemia.
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PMID:Prospective treatment in carnitine-acylcarnitine translocase deficiency. 1750 64

Carnitine-acylcarnitine translocase (CACT) deficiency (McKusick 212138) is a rare life threatening disorder characterized by hypoketotic hypoglycemia, hyperammonemia, encephalopathy, cardiomyopathy hepatopathy, and myopathy. Here, we present a detailed clinical course of 3 Saudi siblings with a severe phenotype. The third patient was described in more detail. Early medical intervention in the form of 25% dextrose intravenous infusion and carnitine supplement followed by a gradual introduction of a high carbohydrate low fat special formula resulted in a good clinical and biochemical response to the treatment in our patient. However, early nephrocalcinosis, severe hypotonia, and subsequently intravascular cerebral accident could not be prevented. He died at 18 months of age as a result of metabolic decompensation. This suggests that CACT deficiency is still a lethal disorder even with an early and aggressive medical intervention.
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PMID:Carnitine-acylcarnitine translocase deficiency. Clinical course of three Saudi children with a severe phenotype. 2130 74

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease of fatty acid oxidation, mainly affecting long chain fatty acid utilization. The disease usually presents at neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy. Definitive diagnosis of CACT deficiency by molecular analysis of the SLC25A20 gene has recently become clinically available. In contrast to biochemical analysis, sequence analysis is a more rapid and reliable method for diagnosis of CACT deficiency. In this study, we used Sanger sequencing and target array CGH to identify molecular defects in the SLC25A20 gene of patients with clinical features and an acylcarnitine profile consistent with CACT deficiency. Eight novel mutations, including a large 25.9 kb deletion encompassing exons 5 to 9 of SLC25A20 were found. Review of the published cases revealed that CACT deficiency is a pan-ethnic disorder with a broad mutation spectrum. Mutations are distributed along the entire gene without a hot spot. Two thirds of them are nonsense, frame-shift, or splice site mutations resulting in premature stop codons. This study underscores the importance of comprehensive molecular analysis, including sequencing and targeted array CGH of the SLC25A20 gene when CACT deficiency is suspected.
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PMID:Expanded molecular features of carnitine acyl-carnitine translocase (CACT) deficiency by comprehensive molecular analysis. 2160 95

In the 1980s, after the mitochondrial DNA (mtDNA) had been sequenced, several diseases resulting from mtDNA mutations emerged. Later, numerous disorders caused by mutations in the nuclear genes encoding mitochondrial proteins were found. A group of these diseases are due to defects of mitochondrial carriers, a family of proteins named solute carrier family 25 (SLC25), that transport a variety of solutes such as the reagents of ATP synthase (ATP, ADP, and phosphate), tricarboxylic acid cycle intermediates, cofactors, amino acids, and carnitine esters of fatty acids. The disease-causing mutations disclosed in mitochondrial carriers range from point mutations, which are often localized in the substrate translocation pore of the carrier, to large deletions and insertions. The biochemical consequences of deficient transport are the compartmentalized accumulation of the substrates and dysfunctional mitochondrial and cellular metabolism, which frequently develop into various forms of myopathy, encephalopathy, or neuropathy. Examples of diseases, due to mitochondrial carrier mutations are: combined D-2- and L-2-hydroxyglutaric aciduria, carnitine-acylcarnitine carrier deficiency, hyperornithinemia-hyperammonemia-homocitrillinuria (HHH) syndrome, early infantile epileptic encephalopathy type 3, Amish microcephaly, aspartate/glutamate isoform 1 deficiency, congenital sideroblastic anemia, Fontaine progeroid syndrome, and citrullinemia type II. Here, we review all the mitochondrial carrier-related diseases known until now, focusing on the connections between the molecular basis, altered metabolism, and phenotypes of these inherited disorders.
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PMID:Diseases Caused by Mutations in Mitochondrial Carrier Genes SLC25: A Review. 3234 Apr 4