Assay of D-lactate in urine of infants and children with reference values taking into account data below detection limit.

Accumulation of D-lactic acid produced by intestinal bacteria such as streptococci and lactobacilli has been extensively studied in ruminants [1-4]. In humans an increased production of D-lactate by intestinal bacteria under pathological conditions such as the short bowel syndrome can cause metabolic acidosis [5-8]. Since the lactate assays routinely used only measure L-lactate we developed a sensitive method of D-lactate quantification and established reference values in spot urines of infants and children (0 to 4 years of age). The enzymatic method with fluorimetric quantification of NADH is linear up to 2 mmol/l. It has a detection limit of 3.4 micromol/l. Among structurally related organic acids an interference was found only for L-lactate and DL-2-hydroxybutyrate at concentrations which are way beyond their physiological excretion. One hundred and sixty five spot urines of healthy Swiss (S), Austrian (A), German (G) and Chilean (CHI) infants aged from 0 to 4 years were analyzed. The distribution of the data is close to a lognormal one. Values below the detection limit were simulated and age groups were formed. In all populations D-lactate excretion was found highest during the first year of life; it declines with age during infancy and remains stable from 2.5 to 4 years of age. We show that D-lactate is excreted physiologically by healthy infants and children below 4 years of age and present reference values for D-lactate excretion which show some differences between the populations tested.

Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population.

OBJECTIVE: To determine reference values for urinary phosphate/creatinine (Cr) concentration ratios and to complete reference values for urinary calcium/creatinine and magnesium/creatinine ratios in the second morning urine sample of healthy infants, children, and adolescents. DESIGN: Urinary P/Cr, Ca/Cr, and Mg/Cr ratios were determined from the second morning urine sample. Two urine samples were obtained 1 week apart from most subjects to assess reproducibility. SETTING: Kindergartens and schools of Lausanne, Switzerland. PARTICIPANTS: A total of 410 healthy children aged 1 month to 17 years (197 girls and 213 boys) participated in the study. RESULTS: The 5th and 95th percentiles were estimated from 664 urine samples. There were no differences related to sex. A nonlinear regression in terms of age was used to smooth the estimated percentiles yielding reference curves from which critical values may be obtained for any given age. The 95th percentile for urinary Ca/Cr and Mg/Cr agreed with previously reported values in children older than 7 years. The upper limit of the three solute/creatinine ratios decreased significantly with age: for urinary P/Cr from 19.0 mol/mol at 1 month to 2.7 at 14 years; for urinary Ca/Cr from 2.2 to 0.7 mol/mol, and for urinary Mg/Cr from 2.2 to 0.6 mol/mol. Lower limits varied little. Interindividual and intraindividual variations decreased with age. CONCLUSIONS: Urinary P/Cr, Ca/Cr, and Mg/Cr ratios vary strongly with age. We provide reference values, expressed both in SI and in mass units, for urinary P/Cr, Ca/Cr, and Mg/Cr in children aged one month to 17 years.

Phenotypic heterogeneity in the syndromes of 3-methylglutaconic aciduria.

Combined 3-methylglutaconic and 3-methylglutaric aciduria, one of the more common urinary organic acid abnormalities, has been observed in at least three clinical syndromes. We studied an additional seven patients with 3-methylglutaconic aciduria, four of whom were best categorized as having the type II syndrome, two as having an "unspecified" syndrome, and one who may have had a primary urea cycle defect. In cultured cells and autopsy tissues derived from patients with the type II and unspecified syndromes, we were unsuccessful in identifying a defect in the leucine degradative pathway distal to 3-methylcrotonyl-coenzyme A carboxylase and in the cholesterol biosynthetic pathway between 3-hydroxy-3-methylglutaryl-coenzyme A reductase and diphosphomevalonate decarboxylase. Further assessment of the cholesterol biosynthetic pathway in several patients with one of the two types of disease also provided no defined abnormality. The primary metabolic defects in the type II and unspecified syndromes remain undefined.