A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market.

The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) started an intensive review of commercially available parenteral vitamin and trace element (TE) products in 2009. The chief findings were that adult multi-TE products currently available in the United States (U.S.) provide potentially toxic amounts of manganese, copper, and chromium, and neonatal/pediatric multi-TE products provide potentially toxic amounts of manganese and chromium. The multivitamin products appeared safe and effective; however, a separate parenteral vitamin D product is needed for those patients on standard therapy who continue to be vitamin D depleted and are unresponsive to oral supplements. The review process also extended to parenteral choline and carnitine. Although choline and carnitine are not technically vitamins or trace elements, choline is an essential nutrient in all age groups, and carnitine is an essential nutrient in infants, according to the Food and Nutrition Board of the Institute of Medicine. A parenteral choline product needs to be developed and available. Efforts are currently under way to engage the U.S. Food and Drug Administration (FDA) and the parenteral nutrient industry so A.S.P.E.N.'s recommendations can become a commercial reality.

Quantification of malonylcarnitine in dried blood spots by use of MS/MS varies by stable isotope internal standard composition.

BACKGROUND: The utilization of MS/MS for the analysis of amino acids and acylcarnitines from dried blood spots (DBS) is routine in many newborn screening (NBS) laboratories. Recently, malonylcarnitine (C3DC) was shown to be elevated in the DBS of affected infants with malonic acidemia. Quantitative features were unknown, so that its measurement was an approximation. Synthesis of malonylcarnitine enabled both a study in the analytical characteristics of C3DC and a survey of its measurement in NBS laboratories. METHODS: Malonylcarnitine was enriched in blood and spotted onto filter paper cards. The DBS were sent to several laboratories for analysis, and the results were returned to the Centers for Disease Control and Prevention (CDC) for evaluation. Reports included a description of the MS/MS method utilized. RESULTS: A pilot proficiency survey shows a bimodal distribution of data from 98 laboratories. Analysis of proficiency data reveals the use of different stable isotope internal standards for quantification. Analysis of standard, labeled or unlabelled ((2)H(3)-octanoylcarnitine (C8), glutarylcarnitine (C5DC) and malonylcarnitine (C3DC) revealed significantly different ion detection values. Quantification in laboratories is based on the ratio of the metabolite in question to a reference stable isotope standard. CONCLUSIONS: Quantification of metabolites depends upon the reference isotope standard utilized. Quantification requires describing the standards used for estimation of concentration (a pseudo-concentration) and a notation that includes a reference to the isotope standard used. This descriptive method will enable harmonization of data in screening laboratories.

Normal acylcarnitine levels during confirmation of abnormal newborn screening in long-chain fatty acid oxidation defects.

We report two infants identified by tandem mass spectrometry (MS/MS) of neonatal blood spot acylcarnitines and confirmed by molecular genetic analysis to have long-chain fatty acid oxidation defects. In both cases, acylcarnitine concentrations in confirmatory plasma samples were normal. None the less, molecular testing identified trifunctional protein (TFP) deficiency (McKusick 600890) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (McKusick 201475).

[Levels of L-carnitine in the Venezuelan infant population]. / Niveles de L-carnitina en la población infantil venezolana.

The L-carnitine blood serum and amniotic fluid levels were measured in 133 samples obtained from clinically healthy patients: 39 pregnant women with a fetal gestational age ranging from 14 to 40 weeks, 13 newborn children less than a day old, 19 newborn children between the ages of 1 and 30 days, 8 breast-feed babies and 19 children over two years of age. No significant statistical differences were seen in the maternal blood serum and amniotic fluid samples for the different gestational ages considered in the study. The average values were found to be 22.6 +/- 5.1 nmol/mL for maternal blood serum and 25.3 +/- 9.4 nmol/mL for amniotic fluid. The blood serum levels were found to be greater in the group between the ages of 1 to 30 days, reaching levels of 43.1 +/- 7.4 nmol/mL. In the group aged 1 month-18 years, the serum levels were on the average 34.3 +/- 6.7 nmol/mL. The variations found among these groups reflect characteristics specific of our population. These values should be further researched since they differ from those values reported by the Anglo-Saxons. L-carnitine concentration; blood serum level; amniotic fluid level.