1/15. Neonatal presentation of ventricular tachycardia and a Reye-like syndrome episode associated with disturbed mitochondrial energy metabolism.BACKGROUND: hyperammonemia, hypoglycemia, hepatopathy, and ventricular tachycardia are common presenting features of carnitine-acylcarnitine translocase deficiency (Mendelian Inheritance in Man database: *212138), a mitochondrial fatty acid oxidation disorder with a lethal prognosis. These features have not been identified as the presenting features of mitochondrial cytopathy in the neonatal period. CASE PRESENTATION: We describe an atypical presentation of mitochondrial cytopathy in a 2 day-old neonate. She presented with a Reye-like syndrome episode, premature ventricular contractions and ventricular tachycardia. Initial laboratory evaluation exhibited a large amount of 3-methylglutaconic acid on urine organic acid analysis, mild orotic aciduria and a nonspecific abnormal acylcarnitine profile. The evaluation for carnitine-acylcarnitine translocase deficiency and other fatty acid oxidation disorders was negative. The patient later developed a hypertrophic cardiomyopathy and continued to be affected by recurrent Reye-like syndrome episodes triggered by infections. A muscle biopsy exhibited signs of a mitochondrial cytopathy. During the course of her disease, her Reye-like syndrome episodes have subsided; however, cardiomyopathy has persisted along with fatigue and exercise intolerance. CONCLUSIONS: This case illustrates that, in the neonatal period, hyperammonemia and ventricular tachycardia may be the presenting features of a lethal carnitine-acylcarnitine translocase deficiency or of a mitochondrial cytopathy, associated with a milder clinical course. This association broadens the spectrum of presenting phenotypes observed in patients with disturbed mitochondrial energy metabolism. Also, the presence of 3-methylglutaconic aciduria suggests mitochondrial dysfunction and mild orotic aciduria could potentially be used as a marker of mitochondrial disease.- - - - - - - - - - ranking = 1keywords = metabolism (Clic here for more details about this article) |
2/15. liver fatty acid-binding protein in two cases of human lipid storage.FABPs in the various tissues play an important role in the intracellular fatty acid transport and metabolism. Reye's syndrome (RS) and multisystemic lipid storage (MLS) are human disorders characterized by a disturbance of lipid metabolism of unknown etiology. We investigated for the first time L-FABP in these two conditions. Affinity purified antibodies against chicken L-FABP were raised in rabbits, and found to cross-react specifically with partially purified human L-FABP. L-FABP content in liver samples of two patients with RS and MLS was investigated by immuno-histochemistry, SDS-PAGE and ELISA. L-FABP immuno-histochemistry showed increased reactivity in the liver of RS patient and normal reactivity in MLS liver. L-FABP increase in RS liver was confirmed by densitometry of SDS-PAGE and ELISA method. By these two methods the increase amounted to 180% and 199% (p less than 0.02), respectively, as compared to controls. A possible role of L-FABP in the pathogenesis of RS is discussed.- - - - - - - - - - ranking = 0.4keywords = metabolism (Clic here for more details about this article) |
3/15. Medium-chain acyl CoA dehydrogenase deficiency: electron microscopic differentiation from reye syndrome.Inborn errors involving the oxidative metabolism of fatty acids may present clinically with a reye syndrome-like picture. This case report of a patient with medium-chain acyl CoA dehydrogenase (MCAD) deficiency illustrates that electron microscopy may help to differentiate this disorder from reye syndrome even if a liver biopsy is performed in a patient who recovered from an acute metabolic decompensation. Together with this case, a review of the few reports in the literature of pathological findings in MCAD deficiency is given. Changes uncharacteristic for reye syndrome are a large-droplet steatosis and the presence of distinctive mitochondrial abnormalities on electron microscopy. The detection of an electron dense mitochondrial matrix and a widened space of inner mitochondrial membranes rules out reye syndrome and is suggestive of a disorder of mitochondrial fatty acid oxidation.- - - - - - - - - - ranking = 0.3099856243115keywords = metabolism, error (Clic here for more details about this article) |
4/15. Medium-chain acyl-coa dehydrogenase deficiency.Medium-chain acyl-coa dehydrogenase (MCAD) deficiency is the most frequently diagnosed defect in fatty acid metabolism and is one of the most common inborn errors of metabolism. diagnosis may be difficult, since the disorder may present as hypoglycemia, sudden infant death syndrome or a Reye's syndrome-like illness. Because of the abrupt clinical deterioration seen with MCAD deficiency, as well as its treatable nature and its genetic implications, this disorder presents a significant challenge for family physicians.- - - - - - - - - - ranking = 7.6524055169777keywords = inborn error, metabolism, error (Clic here for more details about this article) |
5/15. reye syndrome: rate of oxidation of fatty acids in leukocytes and serum levels of lipid peroxides.We examined the oxidation of different chain length fatty acids in the leukocytes and the quantity of lipid peroxides in the plasma of two reye syndrome patients. We have found that the oxidation of [1-14C] octanoic acid in homogenates of leukocytes from one of the reye syndrome patients was only 38 percent of the control, whereas oxidation of [1-14C] palmitic and [1-14C] lignoceric acid was slightly increased. The level of lipid peroxides in the serum of both of the reye syndrome patients was 4.42 and 3.04 times higher than the control level. These results suggest that impaired oxidation of medium chain fatty acids (octanoic acid) and higher levels of lipid peroxides may contribute to the pathogenesis of cellular toxicity in reye syndrome. reye syndrome (RS) was first described by Reye et. al. in 1963 and is now recognized as an important cause of morbidity and mortality in infants and children. The clinical course in RS consists of an antecedent viral illness with subsequent encephalopathy and hepatic dysfunction. Laboratory findings in RS include hypoglycemia, hyperammonemia, free fatty acidemia, elevated organic acids and amino aciduria. The ultrastructural findings in RS patients include changes in mitochondria, smooth endoplasmic reticulum morphology, and an increase in the number of peroxisomes. The elevation of serum free fatty acids in RS and their decrease in patients who improve clinically suggests a disturbance in fatty acid metabolism. To understand the role of free fatty acids in the pathogenesis of RS, we examined the levels of lipid peroxides in plasma and catabolism of fatty acids of different chain lengths in leukocytes from RS patients.- - - - - - - - - - ranking = 0.2keywords = metabolism (Clic here for more details about this article) |
6/15. Inborn errors of metabolism in children referred with Reye's syndrome. A changing pattern.Genetic disorders were identified infrequently among children presenting with Reye's syndrome in the past. During a two-year period, we evaluated four consecutive patients referred for intensive care of Reye's syndrome. A standard investigation for inborn errors of metabolism revealed that two patients had enzymatic defects of fatty acid oxidation, and the other two had partial deficiencies of ornithine transcarbamoylase. None had experienced a previous episode of Reye's syndrome, and three of the four had been entirely healthy in the past. Our experience suggests that as the incidence of Reye's syndrome has decreased, patients with its clinical features are now more likely to have manageable inborn errors of metabolism (eg, disorders of ureagenesis, ketogenesis, and branched-chain amino acids).- - - - - - - - - - ranking = 16.144753531201keywords = inborn error, metabolism, error (Clic here for more details about this article) |
7/15. Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome.The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium-chain or long-chain enzyme activity in cultured skin fibroblasts or in leukocytes. Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro- or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains to be determined.- - - - - - - - - - ranking = 7.2524055169777keywords = inborn error, error (Clic here for more details about this article) |
8/15. Familial Reye-like syndrome: a presentation of medium-chain acyl-coenzyme a dehydrogenase deficiency.A 20-month-old girl with a family history of two siblings who died of an encephalopathy diagnosed as reye syndrome presented to an emergency room in hypoglycemic coma and was found to have medium-chain acyl-coenzyme a dehydrogenase deficiency. The salient clinical and biochemical features of this newly described inborn error of fatty acid metabolism are described and contrasted to those of classical reye syndrome. Important clues that should lead the clinician to suspect this disorder, methods of diagnosis, and appropriate acute and long-term therapy are also discussed.- - - - - - - - - - ranking = 7.4524055169777keywords = inborn error, metabolism, error (Clic here for more details about this article) |
9/15. Altered metabolic profiles of valproic acid in a patient with Reye's syndrome.Urinary valproate metabolite and endogenous organic acid profiles in a 6-yr-old girl with Reye's syndrome were investigated by means of gas chromatography-mass spectrometry. 2-n-Propyl-3-oxovaleric acid, normally the major metabolite of valproate in man, was undetectable, while 2-n-propylglutaric acid, the end product via omega-oxidation was markedly increased. Polyunsaturated valproate was not found. Valproate-glucuronide was still found as the major metabolite. The clinical findings coupled with a greatly increased excretion of lactate and adipate was compatible with Reye's syndrome. ketone bodies were not detectable. This case study shows that Reye's syndrome causes altered valproate metabolism, consistent with the defective mitochondrial beta-oxidation of medium chain fatty acids, and suggests that valproic acid should not be used in the treatment of seizures in patients with this syndrome.- - - - - - - - - - ranking = 0.2keywords = metabolism (Clic here for more details about this article) |
10/15. Identification of fatty acid methyl esters in kidneys and livers of two patients with Reye's syndrome.An unusual lipid, having an Rf value between that of cholesterol ester and of triglyceride on thin-layer chromatography, was clearly demonstrated in lipids from kidneys and livers of two Japenese children with Reye's syndrome. gas chromatography-mass spectrometry revealed that the unusual lipid from viscera of the patients was a mixture of fatty acid methyl esters. Whether the occurrence of fatty acid methyl ester is the result of an inborn error of metabolism common to both patients, who were the progeny of consanguineous marriages, or whether it is a common biochemical feature in Reye's syndrome remains the subject of future studies.- - - - - - - - - - ranking = 7.4524055169777keywords = inborn error, metabolism, error (Clic here for more details about this article) |
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