Atypical Phenylketonuria in Sisters With Normal Offspring

Woolf, L. I.; Ounsted, Christopher; Lee, Douglas S.; Humphrey, Michael; Cheshire, NeilM.; Steed, G. R.

doi:10.1016/s0140-6736(61)92434-5

Cited by 85 publications

(17 citation statements)

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“…JEFFCOATE et al [15] were able to diagnose a case of the adrenogenital syndrome prior to birth by detecting elevated levels of the 17-ketosteroids and of pregnanetriol in amniotic fluid. WOOLF et al [32] have found that the amniotic fluid of a mother who had atypical phenylketonuria with hyperphenylalaninemia, and whox baby was normal, contained a high concentration of phenylalanine.…”

Section: Discussionmentioning

confidence: 99%

Free Amino Acids in Human Amniotic Fluid. A Quantitative Study by Ion-Exchange Chromatography

Levy

Montag

1969

Pediatr Res

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ExtractAmniotic fluid was collected at inductive amniotomy or just prior to delivery following full-term uncomplicated pregnancies. Table I lists the means, ranges, and standard deviations for the concentrations of amino acids obtained by ion-exchange chromatography of 16 specimens of amniotic fluid. Each specimen contained the following 22 amino acids: taurine, aspartic acid, threonine, serine, glutamine, proline, glutamic acid, citrulline, glycine, alanine, a-aminobutyric acid, valine, cystine, methionine, isoleucine, tyrosine, phenylalanine, ornithine, lysine, histidine, and arginine. In addition, tryptophan, which could not be detected by the ion-exchange chromatographic method employed, was found in each specimen by paper chromatography. The amino acids present in amniotic fluid were the same as those found in samples of maternal vein, umbilical artery, and umbilical vein serum (table 11). Comparisons were made in the concentrations of several amino acids among amniotic fluid, maternal serum, umbilical artery and vein serum, and perinatal urine (table 11). Taurine was present in considerably greater concentration in amniotic fluid than in maternal serum. This amino acid is also present in large quantities in umbilical artery and vein serum (table 11) and is by far the greatest single contributor to the total free amino acid pool in perinatal urine [I]. I n contrast, amino acids such as leucine, valine, and threonine, which are present in much smaller amounts in amniotic fluid than in either maternal or umbilical serum, are found in even lower concentrations in perinatal urine [I]. These comparisons suggest that amniotic fluid is derived from at least three sources, maternal blood, fetal blood, and fetal urine, a finding compatible with existing evidence [3, 24, 27, 301.

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Section: Discussionmentioning

confidence: 99%

Free Amino Acids in Human Amniotic Fluid. A Quantitative Study by Ion-Exchange Chromatography

Levy

Montag

1969

Pediatr Res

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“…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).…”

Section: Speculationmentioning

confidence: 99%

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

et al. 1974

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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...

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“…Normally intelligent phenylketonurics have occasionally been found among relatives of typical phenylketonuria patients (Woolf et al 1961, and many others). An extraordinary case (a brother of a typical phenylketonurics) was reported by Isogai et al (1964).…”

Section: Discussionmentioning

confidence: 97%

Genetic effects of maternal inbreeding in man on congenital abnormality, mental defect, infertility, and prenatal death

Tanaka

1977

Jap J Human Genet

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Atypical Phenylketonuria in Sisters With Normal Offspring

Cited by 85 publications

References 0 publications

Free Amino Acids in Human Amniotic Fluid. A Quantitative Study by Ion-Exchange Chromatography

Free Amino Acids in Human Amniotic Fluid. A Quantitative Study by Ion-Exchange Chromatography

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

Genetic effects of maternal inbreeding in man on congenital abnormality, mental defect, infertility, and prenatal death

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