Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU

Spronsen, Francjan J. van; Rijn, M. van; Dorgelo, Bart; Hoeksma, Marieke; Bosch, Annet M.; Mulder, Margot F.; Klerk, J. B. C. de; Koning, Tom de; Rubio‐Gozalbo, M. Estela; Vries, Marianne de; Verkerk, P.H.

doi:10.1007/s10545-008-0937-3

Cited by 38 publications

(36 citation statements)

References 16 publications

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“…Rey et al (1974) first described the influence of age on excretion of OHPAA in children with PKU and found adult threshold values only after 2 years. Accordingly, metabolic data of PKU children older than 2 years conform with respective findings in juvenile patients (Langenbeck et al 1980(Langenbeck et al , 1992, and phe tolerance at 10 years of age can be predicted reliably from the respective data at 2 years (van Spronsen et al 2009). …”

Section: Discussionsupporting

confidence: 72%

“…After description of the 6ML data (Lutz et al 1990;M€ onch et al 1990;Langenbeck et al 2009) and of preliminary results of 5YL (Schmidt et al 1989), we here present for all 5YL study patients the analytical results of phe disposal in blood and of urinary excretion of acidic phe transamination metabolites. Synopsis of the 5YL blood and urine data suggests maturation of phe transamination and/or renal metabolite transport between 6 months and 5 years as the reason for both the predictability of phe tolerance from 2 years on (van Spronsen et al 2009) and reliable classification of PKU/HPA through age 5 phe tolerance data (G€ uttler and Guldberg 1996).…”

Section: Avmentioning

confidence: 99%

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Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age

et al. 2015

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Background: As part of the German Collaborative Study on Phenylketonuria (PKU)/Hyperphenylalaninaemia (HPA) Study Protocol, a Blaskovics protein loading test (180 mg phenylalanine (phe) protein equivalent per kg body weight and day for 72 h) had been applied to 145 children at the age of 6 months. For investigating possible age-related changes of metabolic phenotype, 51 of them received a 2nd loading test at 5 years of age.Methods: Besides the analysis of blood phe levels, acidic phe transamination metabolites were quantified in urine.Results: Compared to the 6-month data, the mean blood phe level 72 h after start of loading (Phe72) was found to be decreased by 7% (P ¼ 0.06), whereas the mean urinary excretion (per 1.73 m 2 body surface and day) of 2-hydroxyphenylacetic acid was increased 1.9-fold (P < 0.01). Corresponding with these analytical data, the kinetic model constant k out of metabolic plus renal phe disposal was found increased 1.3-fold in mean (P < 0.01).In 3 of the 51 patients, Phe72 was very high at 6 months while in the medium range at 5 years, suggesting that catabolic states may mimic a more severe metabolic defect.The blood phe level response of mild PKU (type II) was assigned identically at both ages in 7/9 patients. Diverging results were (i) response type III (mild hyperphenylalaninaemia) at 6 months and type II at 5 years and (ii) type II at 6 months and type III at age 5.Conclusion: Renal elimination of OHPAA and phe tolerance increase significantly between the age of 6 months and 5 years, suggesting that, at least in childhood, formation and/or renal disposal of phe transamination metabolites may be major distal determinants of phe tolerance.

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Section: Discussionsupporting

confidence: 72%

Section: Avmentioning

confidence: 99%

Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age

et al. 2015

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“…Recently it has been shown that Phe tolerance may be predictable already at the age of 2 years, and that Phe tolerance at age 2, 3, and 5 years correlates with that at age 10 years [41]. In contrast, reassessment of Phe tolerance may be necessary in adults [42].…”

Section: Phenylalanine Tolerancementioning

confidence: 99%

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

Blau

Hennermann

Langenbeck

et al. 2011

Molecular Genetics and Metabolism

206

168

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This article summarizes the present knowledge, recent developments, and common pitfalls in the diagnosis, classification, and genetics of hyperphenylalaninemia, including tetrahydrobiopterin (BH4) deficiency. It is a product of the recent workshop organized by the European Phenylketonuria Group in March 2011 in Lisbon, Portugal. Results of the workshop demonstrate that following newborn screening for phenylketonuria (PKU), using tandem mass-spectrometry, every newborn with even slightly elevated blood phenylalanine (Phe) levels needs to be screened for BH4 deficiency. Dried blood spots are the best sample for the simultaneous measurement of amino acids (phenylalanine and tyrosine), pterins (neopterin and biopterin), and dihydropteridine reductase activity from a single specimen. Following diagnosis, the patient's phenotype and individually tailored treatment should be established as soon as possible. Not only blood Phe levels, but also daily tolerance for dietary Phe and potential responsiveness to BH4 are part of the investigations. Efficiency testing with synthetic BH4 (sapropterin dihydrochloride) over several weeks should follow the initial 24-48-hour screening test with 20mg/kg/day BH4. The specific genotype, i.e. the combination of both PAH alleles of the patient, helps or facilitates to determine both the biochemical phenotype (severity of PKU) and the responsiveness to BH4. The rate of Phe metabolic disposal after Phe challenge may be an additional useful tool in the interpretation of phenotype-genotype correlation. This article summarizes the present knowledge, recent developments, and common pitfalls in the diagnosis, classification, and genetics of hyperphenylalaninemia, including tetrahydrobiopterin (BH4) deficiency. It is a product of the recent workshop organized by the European Phenylketonuria Group in March 2011 in Lisbon, Portugal. Results of the workshop demonstrate that following newborn screening for phenylketonuria (PKU), using tandem mass-spectrometry, every newborn with even slightly elevated blood phenylalanine (Phe) levels needs to be screened for BH4 deficiency. Dried blood spots are the best sample for the simultaneous measurement of amino acids (phenylalanine and tyrosine), pterins (neopterin and biopterin), and dihydropteridine reductase activity from a single specimen. Following diagnosis, the patient's phenotype and individually tailored treatment should be established as soon as possible. Not only blood Phe levels, but also daily tolerance for dietary Phe and potential responsiveness to BH4 are part of the investigations. Efficiency testing with synthetic BH4 (sapropterin dihydrochloride) over several weeks should follow the initial 24-48-hour screening test with 20 mg/kg/day BH4. The specific genotype, i.e. the combination of both PAH alleles of the patient, helps or facilitates to determine both the biochemical phenotype (severity of PKU) and the responsiveness to BH4. The rate of Phe metabolic disposal after Phe challenge may be an additional useful tool in the interp...

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“…Long-term BH4 responders and long-term BH4 non-responders were compared according to their maximal Phe plasma concentration and their maximal Phe/tyrosine (Tyr) ratio before start of Phe-restricted diet and on Phe-restricted diet, their Phe tolerance at the age of 3 years [21], their results of neonatal BH4 loading test, and their genotype. These variables were used to compare the predictive value for long-term BH4 responsiveness.…”

Section: Predictive Parametersmentioning

confidence: 99%

Long-term treatment with tetrahydrobiopterin in phenylketonuria: Treatment strategies and prediction of long-term responders

Hennermann

Roloff

Gebauer

et al. 2012

Molecular Genetics and Metabolism

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Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU

Abstract: Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10 years of age, starting at 2 years of age.

Cited by 38 publications

References 16 publications

Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age

Development of Metabolic Phenotype in Phenylketonuria: Evaluation of the Blaskovics Protein Loading Test at 5 Years of Age

Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies

Long-term treatment with tetrahydrobiopterin in phenylketonuria: Treatment strategies and prediction of long-term responders

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