Citrin deficiency in a Romanian child living in Spain highlights the worldwide distribution of this defect and illustrates the value of nutritional therapy.

We report citrin deficiency in a neonatal non-East-Asian patient, the ninth Caucasian reported with this disease. The association of intrahepatic cholestasis, galactosuria, very high alpha-fetoprotein and increased plasma and urine citrulline, tyrosine, methionine and threonine levels suggested citrin deficiency. Identification of a protein-truncating mutation (c.1078C>T; p.Arg360*) in the SLC25A13 gene confirmed the diagnosis. An immediate response to a high-protein, lactose-free, low-carbohydrate formula was observed. Our report illustrates the need for awareness on citrin deficiency in Western countries.

Threonine requirement of parenterally fed postsurgical human neonates.

BACKGROUND: The threonine requirement of human neonates who receive parenteral nutrition (PN) has not been determined experimentally. OBJECTIVE: The objective was to determine the parenteral threonine requirement for human neonates by using the minimally invasive indicator amino acid oxidation technique with L-[1-(13)C]phenylalanine as the indicator amino acid. DESIGN: Nine postsurgical neonates were randomly assigned to 16 threonine intakes ranging from 10 to 100 mg . kg(-1) . d(-1). Breath and urine samples were collected at baseline and at plateau for (13)CO(2) and amino acid enrichment, respectively. The mean threonine requirement was determined by applying a 2-phase linear regression crossover analysis to the measured rates of (13)CO(2) release (F(13)CO(2)) and L-[1-(13)C]phenylalanine oxidation. RESULTS: The mean threonine parenteral requirement determined by using phenylalanine oxidation was 37.6 mg . kg(-1) . d(-1) (upper and lower confidence limits, respectively: 29.9 and 45.2 mg . kg(-1) . d(-1)) and by using F(13)CO(2) oxidation was 32.8 mg . kg(-1) . d(-1) (upper and lower confidence limits, respectively: 29.7 and 35.9 mg . kg(-1) . d(-1)). Graded intakes of threonine had no effect on phenylalanine flux. CONCLUSION: This is the first study to report on the threonine requirement for human neonates receiving PN. We found that the threonine requirement for postsurgical PN-fed neonates is 22-32% of the content of threonine that is presently found in commercial PN solutions (111-165 mg . kg(-1) . d(-1)).

Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats.

Dietary cobalamin (vitamin B12; Cbl) deficiency caused significant increases in plasma serine, threonine, glycine, alanine, tyrosine, lysine and histidine levels in rats. In particular, the serine and threonine levels were over five and eight times, respectively, higher in the Cbl-deficient rats than those in the sufficient controls. In addition, some amino acids, including serine and threonine, were excreted into urine at significantly higher levels in the deficient rats. When Cbl was supplemented into the deficient rats for 2 weeks, in coincidence with the disappearance of the urinary excretion of methylmalonic acid (an index of Cbl deficiency), the plasma serine and threonine levels were normalized. These results indicate that Cbl deficiency results in metabolic disorder of certain amino acids, including serine and threonine. The expression level of hepatic serine dehydratase (SDH), which catalyzes the conversion of serine and threonine to pyruvate and 2-oxobutyrate, respectively, was significantly lowered by Cbl deficiency, even though Cbl does not participate directly in the enzyme reaction. The SDH activity in the deficient rats was less than 20% of that in the sufficient controls, and was normalized 2 weeks after the Cbl supplementation. It is thus suggested that the decrease of the SDH expression relates closely with the abnormalities in the plasma and urinary levels of serine and threonine in the Cbl-deficient rats.