1/11. Glutaric aciduria type II: observations in seven patients with neonatal- and late-onset disease.The clinical, biochemical, and neuroradiologic findings and clinical follow-up of seven patients with glutaric aciduria type II are reported. Three phenotypes of the disease are encountered: neonatal-onset form with congenital anomalies (two patients) or without congenital anomalies (three patients) and late-onset form (two patients). The neonatal-onset form presents as an overwhelming illness, with severe hypoglycemia and metabolic acidosis leading to rapid death. Frequently it is associated with perinatal energy deprivation, a neonate with low birth weight and prematurity. The late-onset form presents with intermittent episodes of vomiting, hypoglycemia, and acidosis especially after meals rich in fat and/or proteins. All parents are consanguineous and have a first- or second-degree relationship. Initially, in the two phenotypes with neonatal onset and during crisis in the late-onset phenotype, routine laboratory evaluation showed severe metabolic acidosis, with an increased anion gap, hypoglycemia without ketonuria, and disturbed liver function tests. In the majority of patients with neonatal-onset forms, the kidneys, liver, and at times the spleen are enlarged with an increased echogenic pattern; however, no hepatic or renal cysts are detected. cardiomegaly is observed in most patients. The diagnosis can be easily and rapidly reached through tandem mass spectrometry study of the blood and can further be confirmed by gas chromatography/mass spectrometry analysis of the urine organic acids. In this report, the magnetic resonance imaging/computed tomography brain studies showed brain atrophy, white matter disease, and in one patient, fluid-filled cavities in the periventricular area and putamina. fluorine-18-labeled 2-fluoro-2-deoxyglucose positron emission tomographic (FDG PET) brain studies in two patients with late-onset disease showed slightly decreased activity in the cerebral cortex in one and in the caudate nuclei in the other. brain FDG PET scan and magnetic resonance spectroscopy were normal in one patient with neonatal-onset disease. All patients were treated with a diet low in fat and protein, oral riboflavin, and carnitine. The results were promising for the late-onset disease. Intravenous carnitine gave rewarding results in one patient with neonatal-onset disease.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/11. Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency.Detailed studies, using gas chromatography and mass spectrometric methods, of the urinary organic acids excreted by a patient with proven pyruvate decarboxylase deficiency are reported. In addition to the greatly-increased levels of lactate and pyruvate, marked elevation in the levels of 2-oxoglutaric, malic, and isocitric acids were observed, with associated increases 2-hydroxyglutaric, fumaric, succinic, and glyceric acids, and reduced citric acid excretion. The levels of excretion during clinically static and acute periods are compared to those in a normal neonate and normal infants. The metabolites observed indicate a probable defect in the oxidation of pyruvate by pyruvate dehydrogenase and suggest the presence of secondary defects in the tricarboxylic acid cycle. Studies of this type may enable the relatively rapid identification of the probable underlying enzyme deficiency in cases of congenital lactic acidosis, prior to confirmatory enzyme studies.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
3/11. Dizygotic twins with 3-hydroxy-3-methylglutaric aciduria; unusual presentation, family studies and dietary management.A 4-month-old infant with hypotonia and macrocephaly was diagnosed as having 3-hydroxy-3-methylglutaric aciduria, using gas chromatography and mass spectrometry and confirmatory enzyme studies. The same diagnosis was made on his asymptomatic non-identical twin. Examination of the pedigree is consistent with an autosomal recessive mode of inheritance. Dietary treatment improved the symptoms of the propositus, but did not prevent episodes similar to Reye's syndrome in both twins. One such episode closely followed immunisation and our experience suggests that children with this disorder should be observed carefully following immunisation. These episodes were accompanied by an overflow of a wide range of abnormal metabolites. Examination of the urine for organic acids should be considered in infants with unexplained hypotonia and macrocephaly, especially if accompanied by abnormal biochemical indices.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
4/11. A case of methylmalonic and propionic acidemia due to methulmalonyl-CoA carbonylmutase apoenzyme deficiency.A patient presenting with a deep metabolic acidosis after birth is described. Gas chromatographic analysis of short chain fatty acid and non volatile organic acids revealed the presence of both propionic and methylmalonic acid. In plasma obtained immediately after death the propionic- and methylmalonic acid concentrations were measured after separation of both acids by thin layer chromatography. The propionic acid concentration was about 5 mM while the methylmalonic acid concentration was 2.6 mM. The methylmalonic acid concentration in urine was 6.8 mM. Propionyl-CoA carboxylase activity measured in leucocytes and liver-mitochondria revealed normal values (53 pmoles/min/mg protein and 6.5 nmoles/min/mg protein respectively). 2-14C-Methyl-malonate oxydation in intact fibroblasts was totally blocked in the patient's cells. The methylmalonyl-CoA carbonyl mutase activity was found to be absent in the patient's fibroblasts. Addition of vit. B12 coenzyme to the incubation mixture stimulated 14C-succinate formation in the control cells but not in the patient's cells.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
5/11. An unusual case of toluene-induced metabolic acidosis.We used gas chromatography-mass spectrometry to analyze serum specimens from a patient whose metabolic ketoacidosis resulted from sniffing a toluene-containing substance; we also analyzed a sample of the abused substance itself and a serum specimen from a normal subject. The blood samples from the patient showed abnormally high concentrations of acetoacetic, azelaic, benzoic, and 3-hydroxybutyric acids, and a smaller amount of hippuric acid than in the control serum. The ketone bodies and benzoic acid appeared to be factors contributing to her acidosis and ketosis. Analysis for volatile solvents in the patient's serum revealed a low concentration of methyl acetate, in contrast to the high concentrations of toluene and bis(2-ethylhexyl) phthalate and the trace concentration of xylene in the abused substance. We consider this case unusual because the presence and concentration of specific ketoacids was unexpected in light of what was known about the patient.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/11. Neonatal 5-oxoprolinuria: difficult-to-diagnose?A male newborn infant presented with metabolic acidosis and haemolytic anaemia. Renal tubular acidosis was suspected in the absence of amino aciduria and the patient was treated with sodium bicarbonate. Two years later, the chronic acidosis, clinical observation of developmental delay and ataxia prompted further investigational studies. 5-Oxoprolinuria was identified by gas-liquid chromatography and confirmed by mass spectrometry after an initial mass spectrum analysis reported a glutamic acid artifact. glutathione and glutathione synthetase in erythrocytes were 25% and 5% of control values, respectively. On the basis of neonatal metabolic acidosis, without amino aciduria and an elevated reticulocyte count, a recommendation is made for blood glutathione and urine 5-oxoproline screening, followed by glutathione synthetase assay for confirmation of neonatal 5-oxoprolinuria.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/11. Excretion of 2-methyl-3-oxovaleric acid in propionic acidemia.A new case of propionic acidemia is presented, paying special attention to the early symptoms of this disease, such as increased drowsiness, muscular hypotonia, poor feeding, hypothermia, metabolic acidosis, ketonuria and vomiting. Investigation by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) revealed the excretion of fairly high amounts of 2-methyl-3-oxovaleric acid, a condensation product of two molecules of propionyl-CoA, as well as the known pathological metabolites such as propionic, 3-hydroxypropionic and methylcitric acids. Among the post mortem findings the histological studies of the liver were the most remarkable.- - - - - - - - - - ranking = 2keywords = chromatography (Clic here for more details about this article) |
8/11. Mitochondrial myopathy with cardiomyopathy, lactic acidosis and response to prednisone and thiamine.Clinical, biochemical and pathological findings are described in a 23-year-old male with a mitochondrial myopathy who had a high-output circulatory state and cardiomyopathy which resulted in cardiac insufficiency 22 years before presentation of the skeletal myopathy. Venous lactate levels were elevated and severe lactic acidosis developed at one stage of the illness. Electron microscopy of muscle tissue showed various mitochondrial abnormalities and accumulation of neutral lipids which was confirmed histochemically and by thin-layer chromatography. Marked improvement in the myopathy occurred after commencement of prednisone and thiamine and was maintained following withdrawal of these drugs. The metabolic defect in this case has not been defined, but an abnormality in the Kreb's over-production of lactate and lipid accumulation in muscle is postulated.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
9/11. Methylmalonic acidemia with the unusual complication of severe hyperglycemia.We describe a case of neonatal methylmalonic acidemia with the unusual complication of severe, insulin-resistant hyperglycemia. Methylmalonic acidemia, an inherited metabolic disease affecting the catabolism of propionic acid, is manifested by persistent metabolic acidosis, urinary excretion of large amounts of methylmalonic acid, and occasionally by hypoglycemia. Severe and persistent metabolic acidosis and hyperglycemia, despite large doses of insulin, were observed in this infant, who excreted large amounts of methylmalonic acid. The diagnosis of methylmalonic acidemia was confirmed by gas chromatography-mass spectroscopy, but the patient died before the defect in glucose tolerance could be delineated. We hypothesize that, in addition to the methylmalonic acidemia, the patient may have had an insulin-receptor defect, which was manifested as an inappropriate response to endogenous and exogenous insulin.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/11. buformin concentrations in a case of fatal lactic acidosis.A fatal case of lactic acidosis in a 84 year old diabetic woman taking buformin is reported. buformin concentrations in serum, other body fluids and tissues were measured by gas chromatography. serum buformin concentration at admission was 5.5 mg/l. Postmortem concentrations were: in serum 3.2 mg/l; in lung 2.8 mg/kg wet weight; in heart 3.0 mg/kg; in pericardial fluid 3.5 mg/l; in liver 5.2 mg/kg; in bile 6.3 mg/l; and in kidney 98 mg/kg.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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