A simple method for detection of heterozygous carriers of the gene for classic phenylketonuria

Hilton, Mary A.; Sharpe, J. Neal; Hicks, Lee G.; Andrews, Billy F.

doi:10.1016/s0022-3476(86)80220-7

Cited by 16 publications

(11 citation statements)

References 15 publications

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“…The analysis of variance between the two groups showed that all parameters except Tyr were significantly high in the heterozygote group; this finding is similar to that of other studies (Rosenblatt and Scriver, 1968;Hilton et al, 1986;Lehmann, 1989).…”

Section: Discussionsupporting

confidence: 91%

“…Plasma Phe levels are expected to be higher in heterozygotes compared with normal homozygotes, while Tyr concentrations will be decreased (Griffin and Etsas, 1975;Hilton et aI., 1986;Lehmann, 1989). The significantly higher plasma Phe levels in heterozygotes found in this study are in agreement with the previous studies (Rosenblatt and Scriver, 1968;Griffin and Elsas, 1975;Hilton et al, 1986). However, mean plasma Tyr levels showed a slight increase in heterozygotes compared with control subjects.…”

Section: Discussionsupporting

confidence: 90%

“…The procedure adopted in this study is simple and adapted to detecting carriers; no Phe loading or venepuncture is required since a single semifasting specimen of only 100 #I of plasma obtained by finger prick is sufficient. The spectrofluorimetric method used for the quantitation of plasma Phe and Tyr levels is much more practical, economical and time-saving than autoanalytical (Blitzer et al, 1986), highperformance liquid chromatographic (Hilton et al, 1986) or DNA analysis (Lehmann, 1989) techniques. The accuracy of the fluorimetric method for the determination of Phe and Tyr has been assessed by the stability of repeated measurements.…”

Section: Discussionmentioning

confidence: 99%

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Heterozygous carriers of classical phenylketonuria in a sample of the turkish population: Detection by a spectrofluorimetric method

Güneral

Ozalp

Tatlidil

1990

J of Inher Metab Disea

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Blood obtained by finger prick from 209 presumed normal homozygotes and 42 heterozygotes for classical PKU was analyzed for plasma phenylalanine (Phe) and tyrosine (Tyr) by a fluorimetric method. Subjects were tested near midday and 3 hours after a protein-rich breakfast. The plot of Phe/Tyr (micromolar ratio) against Phe2/Tyr, permitted the detection of 11 heterozygotes among 209 controls. The accuracy of this method was checked by computation of a stepwise multivariate discriminant analysis, using Phe and Tyr (mumol/L), Phe/Tyr micromolar ratio and Phe2/Tyr as variables. Ten of the 11 subjects were recovered with a percentage of correct classification of over 90%, while one case had a percentage of 89.45%. The PKU gene frequency was found to be 1/19. This emphasizes the importance of a screening programme for PKU gene carrier status in Turkey.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Heterozygous carriers of classical phenylketonuria in a sample of the turkish population: Detection by a spectrofluorimetric method

Güneral

Ozalp

Tatlidil

1990

J of Inher Metab Disea

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“…Although the value of 0.059 mM for normal subjects agrees well with the accepted value of 0.058 Ϯ 0.015 mM (mean and SD) (35), the value of 0.079 mM for heterozygotes who might be expected to have 50% of the normal PAH level, appears to be too low. The ratio of blood phenylalanine levels for controls and for obligate PKU heterozygotes has been reported to be in the range of 1.57-1.61 (36)(37)(38) rather than the ratio of 1.34 that was predicted by the model. This calculated value raises the possibility that PKU heterozygotes may have less than 50% of control PAH activity.…”

Section: ϫDphe͞dt ϭ ϫVmentioning

confidence: 89%

A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients

Kaufman

1999

Proc. Natl. Acad. Sci. U.S.A.

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The derivation of a quantitative model of phenylalanine metabolism in humans is described. The model is based on the kinetic properties of pure recombinant human phenylalanine hydroxylase and on estimates of the in vivo rates of phenylalanine transamination and protein degradation. Calculated values for the steady-state concentration of blood phenylalanine, rate of clearance of phenylalanine from the blood after an oral load of the amino acid, and dietary tolerance of phenylalanine all agree well with data from normal as well as from phenylketonuric patients and obligate heterozygotes. These calculated values may help in the decision about the degree of restriction of phenylalanine intake that is necessary to achieve a satisfactory clinical outcome in classical patients and in those with milder forms of the disease.The initial and rate-limiting step in the complete catabolism of phenylalanine to CO 2 and water is its hydroxylation to tyrosine, a reaction catalyzed by the phenylalanine hydroxylating system. The system is complex, consisting of phenylalanine hydroxylase (PAH), the pterin coenzyme tetrahydrobiopterin (BH 4 ), and several enzymes that serve to regenerate BH 4 , i.e., dihydropteridine reductase and pterin 4␣-carbinolamine dehydratase (1, 2).Although the benzene ring of phenylalanine cannot be ruptured without first being hydroxylated in the para position, the alanine side-chain of the amino acid can be metabolized even in the absence of the ring-hydroxylation step. This alternate pathway is initiated by transamination of phenylalanine to phenylpyruvate followed by conversion of the latter compound to metabolites such as phenyllactate, phenylacetate, and o-hydroxyphenylacetate.

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“…These findings are in line with previous studies. 18,24 In the heterozygote group, the mean value of Phe, Phe/Tyr, and Phe 2 /Tyr reached the peak at T45, suggesting that the metabolization of Phe into Tyr was slower for this group compared to the control group. In accordance, Tyr levels were higher at T60.…”

Section: Discussionmentioning

confidence: 92%

Phenylalanine and Tyrosine Metabolism Analysis in Heterozygotes for Phenylketonuria and in Healthy Individuals

Andrade

Monteiro

Cruz

et al. 2015

Journal of Inborn Errors of Metabolism and Screening

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Phenylketonuria (PKU) is an inherited metabolic disorder derived from a deficiency in the enzyme phenylalanine hydroxylase, which converts the amino acid phenylalanine (Phe) into tyrosine (Tyr). Here we aimed to examine the metabolism of Phe and Tyr in heterozygotes for PKU during fasting and after oral overload of Phe (25 mg/kg). Plasma concentration of Phe and Tyr and Phe 2 -Tyr ratio were determined under fasting condition or 30, 45, 60, and 90 minutes after Phe overload. The sample consisted of 50 participants: 23 heterozygotes for PKU (10 men and 13 women) and a control group of 27 healthy individuals (13 men and 14 women). The dosage of Phe at 45 and 90 minutes and the micromolar fraction of Phe 2 /Tyr after 90 minutes of overload efficiently differentiated PKU heterozygotes. The discriminant function revealed 86% of accuracy. In fact, 94.4% of heterozygotes for PKU were correctly classified.

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A simple method for detection of heterozygous carriers of the gene for classic phenylketonuria

Cited by 16 publications

References 15 publications

Heterozygous carriers of classical phenylketonuria in a sample of the turkish population: Detection by a spectrofluorimetric method

Heterozygous carriers of classical phenylketonuria in a sample of the turkish population: Detection by a spectrofluorimetric method

A model of human phenylalanine metabolism in normal subjects and in phenylketonuric patients

Phenylalanine and Tyrosine Metabolism Analysis in Heterozygotes for Phenylketonuria and in Healthy Individuals

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