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Biomedical subjects

L Sweetman

Publications and source records attributed to L Sweetman.

At least 109 records · Page 6Linked to original sources
PubMed1984

Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.

A 6-year-old boy presented with recurrent coma associated with hyperammonemia and infection is reported. A liver biopsy revealed decreased ornithine transcarbamylase (OTC) activity (16% of normal). The enzymatic abnormality in the child is supported by the finding of elevated orotic acid excretion in his mother following a protein load, compatible with an X-linked pattern of inheritance. Since initiation of a dietary arginine supplement, the child has not had recurrent episodes of hyperammonemia.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Stable isotope dilution analysis of galactitol in amniotic fluid: an accurate approach to the prenatal diagnosis of galactosemia.

A stable isotope dilution assay for galactitol in amniotic fluid has been developed using selected ion monitoring chemical ionization gas chromatography-mass spectrometry of the hexaacetate derivative. [1,1-2H2]Galactitol was synthesized for use as the internal standard. Galactitol is a component of normal amniotic fluid with a mean concentration of 0.70 +/- 0.18 mumol/liter (n = 5). The amniotic fluid of a fetus with galactosemia had a concentration of 7.96 mumol/liter. Mannitol, sorbitol, and inositol were also found to be normal constituents of amniotic fluid. This stable isotope dilution assay is a rapid accurate method for measurement of galactitol in amniotic fluid for prenatal diagnosis of galactosemia.

Amniotic Fluid↗
PubMed1984

Identification of methyl-branched chain dicarboxylic acids in amniotic fluid and urine in propionic and methylmalonic acidemia.

3-Methyladipic, 4-methylpimelic, 4-methylsuberic, pimelic, and azeleic acids were identified by gas chromatography-mass spectrometry in the amniotic fluid of fetuses with propionic acidemia. These compounds were virtually undetectable in normal amniotic fluid. Concentrations much higher than those of the amniotic fluid were found in the urine of neonatal infants with propionic acidemia and methylmalonic acidemia. It appears that the accumulation of these compounds is a consequence of the accumulation of propionyl-CoA. Evidence was obtained for the presence of other methyl-branched chain dicarboxylic acids. 4-Methylpimelic acid and 4-methylsuberic acid have not previously been identified in human physiological fluids.

Amniotic Fluid↗
PubMed1984

3-Hydroxy-3-methylglutaric aciduria.

3-Hydroxy-3-methylglutaric aciduria was found in a newborn infant whose parents are first cousins. The patient presented at 5 days of life with hyperammonemia, hypoglycemia, and metabolic acidosis. There was no ketonuria. Diagnosis was made by analysis of the pattern of organic acids excreted in the urine. A profound deficiency in activity of 3-hydroxy-3-methylglutaryl-coenzyme A lyase was found in cultured skin fibroblasts. The parents had intermediate levels of enzyme activity.

Cells, Cultured↗
PubMed1984

Succinic semialdehyde dehydrogenase deficiency.

A coupled assay using [14C]4-aminobutyric acid and a direct assay using [14C]succinic semialdehyde have been designed to assay te activity of succinic semialdehyde dehydrogenase in a patient with 4-hydroxybutyric aciduria and family members. In the coupled assay less than 3% of control succinic semialdehyde dehydrogenase activity was found in lysates of lymphocytes isolated from whole blood of the patient. In the direct assay there was no detectable activity of the enzyme in lysates of isolated lymphocytes or cultured lymphoblasts. Results indicated the parents to be heterozygous carriers carriers of the abnormal gene, consistent with an autosomal recessive inheritance.

Adult↗
PubMed1984

Genetic complementation analysis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency in cultured fibroblasts.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency is an inherited metabolic disorder of leucine catabolism showing variability in clinical expression. We have examined the possibility of a biochemical and genetic basis for this heterogeneity by measuring the residual enzyme activities in fibroblast cultured from seven patients. The mean activity of HMG-CoA lyase was 1.1% +/- 0.3% of normal with no significant differences between the patients. Genetic complementation was studied in heterokaryons obtained by fusion with polyethylene glycol using the incorporation of 1-[14C]isovaleric acid into trichloroacetic acid precipitable material to determine the activity of the leucine catabolic pathway. Unfused cells from the patients with a deficiency of HMG-CoA lyase had incorporations of less than 5% of normal. Unfused cells from patients with isovaleric acidemia or a deficiency of 3-methylcrotonyl-CoA carboxylase also had incorporations of less than 5% of normal, and when fused with cells of patients with a deficiency of HMG-CoA lyase, gave positive complementation with an incorporation of 30% of normal. None of the fusions between the seven different lines deficient in HMG-CoA lyase resulted in increased incorporation. Thus, no evidence was obtained for biochemical or genetic heterogeneity in fibroblasts of these seven patients with a deficiency of HMG-CoA lyase that would account for their different clinical presentations.

Cell Fusion↗
PubMed1983

Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism.

Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 +/- 1.9 pmol . min-1 . mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol . min-1 . mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.

4-Aminobutyrate Transaminase↗
PubMed1983

Enzymatic preparation of radiolabeled succinic semialdehyde.

[U-14C]Succinic semialdehyde was prepared with yields of 30-40% by oxidation of purified [U-14C]4-aminobutyric acid with commercially available bovine plasma monoamine oxidase. [U-14C]Succinic semialdehyde was purified by cation-exchange chromatography and quantified as the oxime and methoxime derivatives using liquid partition chromatography on silicic acid. The availability of [U-14C]succinic semialdehyde permits the reliable assay of succinic semialdehyde dehydrogenase in crude cell extracts of lymphocytes isolated from human blood, cultured human lymphoblasts, and other tissues where 4-aminobutyric acid metabolism is known to occur.

Animals↗
PubMed1982

3-hydroxy-3-methylglutaric aciduria: a new assay of 3-hydroxy-3-methylglutaryl-coa lyase using high performance liquid chromatography.

A new assay has been developed for 3-hydroxy-3-methylglutaryl-CoA lyase, the final enzyme in the leucine degradative pathway. The assay was performed by incubating lysates of fibroblasts with [glutaryl-3-14C](D,L)-3-hydroxy-3-methyl-glutaryl coenzyme A. The products were analysed by high performance liquid chromatography with continuous liquid scintillation counting. This provided simultaneous identification and quantification of one of the enzymatic products, [3-14C]acetoacetic acid. The mean 3-hydroxy-3-methylglutaryl-CoA lyase activity in fibroblasts from five controls was 732 +/- 81 (SD) pmol/min X mg protein. Using this assay, we have studied skin fibroblasts cultured from a patient with 3-hydroxy-3-methylglutaric aciduria and found 3% of normal 3-hydroxy-3-methylglutaryl-CoA lyase activity. The activities in skin fibroblasts cultured from the parents were 46 and 53% of control activity which is consistent with heterozygocity. Kinetic studies of 3-hydroxy-3-methylglutaryl-CoA lyase in skin fibroblasts cultured from two normal subjects yielded Km values of 14.4 and 18.8 mumol/l for 3-hydroxy-3-methylglutaryl-CoA.

Acetoacetates↗
PubMed1982

Organic aciduria in neonatal multiple carboxylase deficiency.

A Samoan patient and a Saudi-Arabian patient were found to have abnormalities in the pattern of organic acid metabolites characteristic of 3-methylcrotonylglycinuria, propionic acidaemia and lactic acidosis. Both patients died early in life. The metabolic pattern is diagnostic of multiple carboxylase deficiency and an enzymatic diagnosis was made in a subsequent affected sibling of the first patient. Deficiency of the three carboxylases suggests a primary defect in the metabolism of biotin which is required for their activity. The importance of the recognition of the clinical picture is highlighted by the fact that this lethal disease is readily treated with biotin. These patients have prominent skin lesions which can serve as alerting signs for the diagnosis.

Carboxylic Acids↗
PubMed1981

New metabolites in isovaleric acidemia.

Two metabolites, 4-hydroxyisovaleric acid and mesaconic acid, have been identified and quantified in the urine of a patient with isovaleric acidemia. These compounds do not appear to have been reported previously as being components of human metabolism. In addition, large quantities of 3-methylbutyrolactone, the lactone of 4-hydroxyisovaleric acid, were observed in the volatile profile obtained by headspace chromatography. The demonstration of 4-hydroxyisovaleric acid supports the contention that urinary methylsuccinic acid seen in patients with isovaleric acidemia has arisen by omega-oxidation of isovaleric acid. The identification of mesaconic acid may indicate that the methylsuccinic acid formed in these patients is subject to further metabolism.

4-Butyrolactone↗
PubMed1981

Two forms of biotin-responsive multiple carboxylase deficiency.

Biotin-responsive multiple carboxylase deficiencies are classified into early and late forms. The early form showed higher urinary excretion of 3-hydroxyisovalerate and 3-hydroxypropionate than the late form and was associated with normal plasma biotin concentrations. It is proposed that holocarboxylase synthetase and intestinal biotin absorption are defective in the early and late forms respectively.

Acute Disease↗