Plasma total odd-chain fatty acids in the monitoring of disorders of propionate, methylmalonate and biotin metabolism

WOS: A1996VY55200006PubMed ID: 8982947Total plasma odd-numbered long-chain fatty acids were analysed in patients with methylmalonic acidaemia (vitamin B-12-responsive and unresponsive), combined methylmalonic acidaemia/homocystinuria (CblC), propionic acidaemia (both neonatal-onset and late-onset), biotinidase deficiency and holocarboxylase synthase deficiency, as well as in hospital controls. Total odd-numbered long-chain fatty acids (C-15:0, C-17:1 and C-17:0) were expressed as a percentage of total C-12-C-20 fatty acids. Control values were 0.72% +/- 0.31% (n = 12). Normalization of the percentage of odd-chain fatty acids occurred in all vitamin-responsive patients, following the institution of vitamin treatment. In general the neonatal-onset propionic acidaemia and B-12-unresponsive methylmalonic acidaemia patients had the highest plasma odd-chain fatty acid concentrations, which correlated with the clinical condition but not with the urinary excretion of methylcitrate or methylmalonate. Plasma odd-chain fatty acid concentrations and methylmalonate excretions in CblC patients reacted very well to vitamin B-12 treatment, but with no clinical response. Measurement of plasma odd-chain fatty acids is of no value for the monitoring of defects of biotin metabolism

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(-1) day(-1); n = 4 1), 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 I 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.</p

Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib)

CDG-Ib is the "gastro intestinal'' type of the congenital disorders of glycosylation (CDG) and a potentially treatable disorder. It has been described in patients presenting with congenital hepatic fibrosis and protein losing enteropathy, The symptoms result from hypoglycosylation of serum- and other glycoproteins, CDG-Ib is caused by a deficiency of mannose-6-phosphate isomerase (synonym: phosphomannose isomerase, EC 5.3.1.8), due to mutations in theMPI gene. We determined the genomic structure of the MPI gene in order to simplify mutation detection, The gene is composed of 8 exons and spans only 5 kb. Eight (7 novel) different mutations were found in seven patients with a confirmed phosphomannose isomerase deficiency, analyzed in the context of this study: six missense mutations, a splice mutation and one insertion. In the last, the mutation resulted in an unstable transcript, and was hardly detectable at the mRNA level. This emphasizes the importance of mutation analysis at. the genomic DNA level. Hum Mutat 16:247-252, 2000. (C) 2000 Wiley-Liss, Inc