Aromatic Acids in Urine of Healthy Infants, Persistent Hyperphenylalaninemia, and Phenylketonuria, before and after Phenylalanine Load

Abstract

ExtractAromatic acids in urine were studied by gas chromatography and mass spectrometry in 3 premature and 7 full term healthy infants, in 2 patients with persistent hyperphenylalaninemia, and in 11 patients with phenylketonuria. Eleven aromatic acids were determined quantitatively.On a free diet, patients with phenylketonuria excreted large amounts of phenylacetic, mandelic, phenyllactic, o-OHphenylacetic, and phenylpyruvic acids ("phenylketonuria metabolites"), whereas the two patients with persistent hyperphenylalaninemia showed only a slightly abnormal excretion of these compounds. No or only very small amounts of phenylketonuria metabolites were found in healthy infants on normal diet, as well as in patients with persistent hyperphenylalaninemia or phenylketonuria on low phenylalanine diet.After an oral L-phenylalanine load (100 mg/kg) n o or only a slight increase of phenylketonuria metabolites was observed in the urine during the subsequent 24 h r in healthy infants o n normal diet, as well as in the two patients with persistent hyperphenylalaninemia o n low phenylalanine diet; in contrast, the concentration of these metabolites increased markedly in patients with phenylketonuria on low phenylalanine diet. This divergent response of the aromatic acids in urine to an oral phenylalanine load administered during a low phenylalanine diet probably represents a useful criterion for the differential diagnosis of these t w o conditions. SpeculationThe quantitative determination of the aromatic acids in urine before and after phenylalanine load can be considered as an indirect measurement of phenylalanine hydroxylase activity.after birth and remains subsequently mostly between 4 and 15 mg/100 ml. On a normal protein intake, it only rarely rises t o 20 or more mg/100 ml. The urine tests for aromatic acids (FeC13, DNPH, Phenistix) are usually negative and, with few exceptions (1,14,28,36), o-OH-phenylacetic acid as well as phenylpyruvic acid are not detectable by paper chromatography (12,17,29,30) or spectrophotometry (1). However, abnormal amounts of aromatic acids can always be demonstrated after a phenylalanine load (1,17,24,28,30,35,36). Most patients, whether o n or off a diet, perform within the average range of intelligence (3).Persistent hyperphenylalaninemia has t o be distinguished from other disorders of phenylalanine metabolism such as phenylalanine transaminase deficiency and transient hyperphenylalaninemia (see reviews in References 1 3 and 23). Patients with persistent hyperphenylalaninemia probably represent a biochemically and genetically heterogeneous group.In the present study, aromatic acids in urine were determined quantitatively by gas chromatography and identified by mass spectrometry. The investigation was performed in healthy infants, as well as in patients with persistent hyperphenylalaninemia and phenylketonuria, before and after a phenylalanine load. The patients were studied while on and off a low phenylalanine diet. SUBJECTS AND METHODSAromatic acid excretion in urine was studied in 3 h...

Evaluation of the serum metabolome of patients with alkaptonuria before and after two years of treatment with nitisinone using LC‐QTOF‐MS

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In vivo disposal of phenylalanine in phenylketonuria: A study of two siblings

“…In contrast, subject 2 had higher plasma level of transamination metabolites. It has been a long-standing question whether phenylalanine transamination metabolite accumulation contributes to the neurotoxicity (Rampini 1974;Kaufman 1989;Langenbeck et al 1992), although in this study neither subject achieved metabolites in the toxic range. The difference in renal excretion of the metabolites constitutes a difference of 6#mol/kg per h, which is greater in subject 1 and approximates to 305 mg of phenylalanine per day.…”

Atypical cases of phenylketonuria

“…Various types of phenylalanine loading tests have been developed [7,31,35,36,44], including oral or intravenous tests and deuterium labeling tests. Measurements of phenylalanine and tyrosine levels and urinary aromatic acids have been evaluated as ways to distinguish between PKU and HPA.…”