Metabolic Studies of Transient Tyrosinemia in Premature Infants

Abstract

Extract metabolism. Several follow-ur, studies of infants known t oThe recently developed technique of gas chromatographymass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted t o demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5-10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Several infants had fluctuating levels of tyrosine metabolites in urine although dietary protein intake remained constant a t 3-4 g/kg/24 hr and ascorbic acid at 50 mg/24 hr. Late metabolic acidosis was seen in four infants, but bore n o relation to transient tyrosinemia. The ratio of net acid t o urea excretion in urine increased with increasing base deficit, implying a nonprotein origin of the metabolic acid. No unique metabolic patterns were characteristic of late metabolic acidosis. SpeculationAdvances in gas chromatography-mass spectrometry-computer technology (GC-MS-computer) allow for the screening of body fluids for a wide variety of compounds of biologic importance. One application of this technique is for the investigation of the nutritional adequacy of diets for premature infants. Clinical use of these tools may help establish parameters for assessment of nutrition and allow for a rationalization of diet.There appear to be several defects and disturbances in the metabolism of tyrosine variously grouped under the names tvrosinemia. tvrosinosis. and tyrosyluria (1 7). One such have suffered from transient tyrosinemia could not discern any harmful effects on neurologic or physical development in the first 2 years of life (21, 23). Recently, a long term follow-up study showed that the ultimate intellectual performance, particularly perceptual parameters, may be impaired in some low birth weight infants who had transient tyrosinemia in the neonatal period (22).Late metabolic acidosis (LMA) of the premature, a disturbance of acid-base balance, has been well described in the literature (2, 4,9,13,14,24,(26)(27)(28). We were impressed with several parallels between LMA and transient tyrosinemia. Both occur in prematures at 2-4 weeks of age. Severity and incidence are affected by protein intake and respond favorably t o dietary management. Both are insidious without major symptoms and yet may adversely affect ultimate intellectual outcome.The recently developed technique of GC-MS-computer has made considerable improvements to the tractability and specificity of the chemical analysis of physiologic fluids. It is now possible t o identify and simultaneously quantitate many metabolites and to construct reliable profiles for various groups of compounds so that they might be used t o characterize particular disease states (2, 4 , 9). The technique ha...

Measurement of hepatic phenylalanine metabolism in children using the [13C]-phenylalanine breath test and gas chromatography–mass spectrometry

“…In addition, as phenylalanine hydroxylase prevails even in the fetal liver, deficiencies of certain enzymatic systems and coenzymes of preceding pathways leading to this enzyme are the usual factors in children having PA hypometabolism [22]. As such, although dynamic changes are manifested in individual enzymes related with PA and tyrosine metabolism, current knowledge on changes in the enzymatic systems and development of metabolic pathways in living systems (in vivo) remains ambiguous.…”

Transient neonatal tyrosinemia: a frequent abnormality

“…O coeficiente de correlação linear (r=0,007) calculado pelos valores de fenilalanina e tirosina sugere que a elevação dos níveis de fenilalanina não está necessariamente associada aos valores de tirosina nesses pacientes. Todos os pacientes estudados neste trabalho tiveram seus níveis séricos normalizados após algum tempo, o que pode estar relacionado com a administração de vitamina C e/ou restrição protéica, de acordo com dados previamente relatadas na literatura 25,26 . O mecanismo de ação da vitamina C está relacionado à inativação da phidroxifenilpiruvato oxidase hepática pelo seu próprio substrato, condição esta que pode ser prevenida de forma inespecífica pelo aumento da concentração do ascorbato sérico 27 .…”

13C‐phenylalanine breath test correlates with liver fibrosis in postoperative biliary atresia

“…However, transient hyperphenylalaninemia and hypertyrosinemia are occasionally encountered in children due to the incomplete development of amino acid metabolism, especially PA and tyrosine metabolism 13,14 . Hitherto, we have conducted PBT in children, and although premature PA metabolism is typical of children, hepatic phenylalanine metabolism probably elevated gradually during infancy to eventually establish the adult level at the age of 5–7 years 2,15 .…”