69 research outputs found
Differential diagnosis of (inherited) amino acid metabolism or transport disorders
__Abstract__
Disorders of amino acid metabolism or transport are most clearly expressed in urine. Nevertheless the interpretation of abnormalities in urinary amino acid excretion remains difficult. An increase or decrease of almost every amino acid in urine can be due to various etiology. To differentiate between primary and secondary aminoacido-pathies systematic laboratory investigation is necessary. Early diagnosis of disorders of amino acid metabolism or transport is very important, because most of them can be treated, leading to the prevention of (further) clinical abnormalities. In those disorders, which cannot be treated, early diagnosis in an index-patient may prevent the birth of other siblings by means of genetic counseling and prenatal diagnosis. Primary aminoacidopathies can be due to genetically determined transport disorders and enzyme deficiencies in amino acid metabolism or degradation. Secondary aminoacidopathies are the result of abnormal or deficient nutrition, intestinal dysfunction, organ pathology or other metabolic diseases like organic acidurias. A survey of amino acid metabolism and transport abnormalities will be given, illustrated with metabolic pathways and characteristic abnormal amino acid chromatograms
Functional hyperactivity of hepatic glutamate dehydrogenase as a cause of the hyperinsulinism/hyperammonemia syndrome: effect of treatment
Prenatal diagnosis of morquio disease type A using a simple fluorometric enzyme assay
A new fluorogenic substrate, 4 methylumbelliferyl B-D-6-sulphogalactoside, was used for the
assay of galactose-6-sulphate sulphatase activity in chorionic villi, cultured villus cells, and
amniocytes. The fluorometric assay is much more convenient than the conventional assay
using radiolabelled, sulphated oligosaccharides. Both types of substrate were used in the
prenatal diagnosis of three pregnancies at risk for Morquio type A disease using amniocytes.
These enzyme tests, as well as electrophoresis of glycosaminoglycans in the amniotic fluid,
indicated affected fetuses in two pregnancies and a non-affected fetus in one
Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial
OBJECTIVE: To assess the effect of isocaloric isonitrogenous parenteral
glutamine supplementation on intestinal permeability and nitrogen loss in
newborns and infants after major digestive-tract surgery. SUMMARY
BACKGROUND DATA: Glutamine supplementation in critically ill and surgical
adults may normalize intestinal permeability, attenuate nitrogen loss,
improve survival, and lower the incidence of nosocomial infections.
Previous studies in critically ill children were limited to
very-low-birthweight infants and had equivocal results. METHODS: Eighty
newborns and infants were included in a double-blind, randomized trial
comparing standard parenteral nutrition (sPN; n = 39) to
glutamine-supplemented parenteral nutrition (GlnPN; glutamine target
intake, 0.4 g kg day; n = 41), starting on day 2 after major
digestive-tract surgery. Primary endpoints were intestinal permeability,
as assessed by the urinary excretion ratio of lactulose and rhamnose
(weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary
3-methylhistidine excretion (day 5). Secondary endpoints were mortality,
length of stay in the ICU and the hospital, number of septic episodes, and
usage of antibiotics and ICU resources. RESULTS: Glutamine intake
plateaued at 90% of the target on day 4. No differences were found between
patients assigned sPN and patients assigned GlnPN regarding any of the
endpoints. Glutamine supplementation was not associated with adverse
effects. CONCLUSIONS: In newborns and infants after major digestive-tract
surgery, we did not identify beneficial effects of isonitrogenous,
isocaloric glutamine supplementation of parenteral nutrition. Glutamine
supplementation in these patients therefore is not warranted until further
research proves otherwise
Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles
Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of “null” alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals
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