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Background/Objectives:: Nutritional deficiencies are frequently observed when treating patients with inborn errors of metabolism due to an unbalanced diet. Thus far, patients with isovaleric acidemia (IVA) who adhere to a restricted protein diet have not been investigated in this respect. We hypothesize that these patients may have a polyunsaturated fatty acid (PUFA) deficiency, leading to potential clinical complications. Subjects/Methods:: We examined the nutritional status by reporting on potential deficiencies in PUFAs in treated IVA patients. A general clinical chemistry work-up as well as gas chromatography flame ionization detector analysis was performed to determine PUFAs in the plasma of 10 IVA patients. Results:: The general clinical chemistry tests did not indicate severe hematological abnormalities or nutritional insufficiencies. We identified a significant reduction in plasma PUFA levels, especially in omega-3 (all acids, P<0.001) and omega-6 (in particular 20:3n-6 P<0.0001 and 20:4n-6 P=0.0005) fatty acids. In addition, an elevation in omega-9 fatty acids, with the exception of 20:3n-9 and C22:1n-9, was not suggestive of complete essential fatty acid deficiency but rather indicative of isolated and/or combined omega-3 and omega-6 fatty acid depletion. Conclusions:: This study emphasizes the potential nutritional insufficiencies that may occur because of therapeutic intervention in IVA.

AbstractTracers and kinetic modelling provide the opportunity to follow the movement and to quantify the metabolic fates of biological compounds in vivo. For studies in children and for repeated studies in adults, the use of stable isotopically labelled substrates are preferable and safe. Measurement of isotopic enrichment in biological molecules is highly specific and can be extremely precise. This allows the development of models of biological system dynamics in cells and organs that are otherwise inaccessible for sampling. Applications in biochemistry, nutrition and clinical medicine show the potential of stable isotopes in vivo. Methodology is of paramount importance and includes the choice of bolus studies, (primed) continuous infusions, use of multiple tracers and use of isotopomer information and intrinsic labels. There is no limit to the number and kind of compounds that can be traced. Topics include intermediate metabolism (lipids, proteins and carbohydrates) using hydrogen, carbon and nitrogen labels. In clinical medicine, 13C-breath tests are available for detection of Helicobacter pylori([13C]urea breath test), and for assessment of a variety of gastro-intestinal and hepatic functions (e.g.[13C]octanoate and mixed [13C]triglyceride breath tests for studies of gastric emptying and fat absorption, respectively). Because theoretical, methodological, physiological and practical aspects are intertwined, in vivoresearch with stable isotopes demands close collaboration between the clinical researcher and the chemist responsible for the mass spectrometry.

Summary Quantitative analysis of the following peroxisomal metabolites is reported: very long-chain fatty acids (VLCFA), pipecolic acid, bile acid intermediates, phytanic and pristanic acid, in plasma, urine, cerebrospinal fluid (CSF), blood spots collected at neonatal screening and amniotic fluid. An overview is given of the concentrations of these metabolites in body fluids from control subjects and all patients investigated so far in this laboratory. The method of choice is gas chromatography — mass spectrometry (GC-MS) with electron capture detection, combined with the use of stable-isotope-labelled internal standards

Quantitative analysis of the following peroxisomal metabolites is reported: very long-chain fatty acids (VLCFA), pipecolic acid, bile acid intermediates, phytanic and pristanic acid, in plasma, urine, cerebrospinal fluid (CSF), blood spots collected at neonatal screening and amniotic fluid. An overview is given of the concentrations of these metabolites in body fluids from control subjects and all patients investigated so far in this laboratory. The method of choice is gas chromatography — mass spectrometry (GC-MS) with electron capture detection, combined with the use of stable-isotope-labelled internal standards

A bank of well-characterized CSF has been established by collecting and storing (— 70 °C) CSF samples remaining after completion of routine clinical studies. Over 1, 700 individual patient samples were collected during a 12-month period. A database derived largely from information downloaded from existing hospital-based systems includes the results of individual CSF laboratory studies, in addition to the patient age, primary diagnoses, and details of any malignancy. CSF control material is used to verify storage conditions. The CSF bank supplies investigators with CSF handled in a standardized manner for more precise investigation of CNS disease.

Objectives: To investigate protein metabolism and urea production in preterm small for gestational age (SGA) neonates fed a preterm formula (PF) or fortified human milk (FHM).Methods: Ten preterm SGA neonates were fed either their own mothers milk, fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1–13C]valine. Urea production was determined from steady-state [13C]urea kinetics.Results: Protein intakes were 24% higher in the PF group than in the FHM group. Both kinetic methods showed no difference in protein turnover, synthesis and breakdown between the two groups, but protein accretion was 71–79% higher in the PF group than the FHM group (significance at p<0,05). Urea production rates were not different between the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics.Conclusions: Both PF and FHM appear equally well tolerated by preterm SGA neonates, but protein accretion is higher in the PF group. It is speculated that even SGA preterm infants tolerate higher protein intakes that may improve their early postnatal growth. Protein intake from human milk source will vary but in practice it seems that even SGA preterm infants would benefit from human milk feeding fortified with a higher amount of protein than 0.7 g. per 100ml. In preterm SGA infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.

Isopropenylacetylene (I) is metallated to give the bislithio compound (III) which reacts with various electrophiles such as (IV) to form the enyne derivatives (V).