Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes

MacLeod, Erin; Gleason, Sally T.; Calcar, Sandra C. Van; Ney, Denise M.

doi:10.1016/j.ymgme.2009.07.016

Cited by 45 publications

(44 citation statements)

References 37 publications

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“…In contrast, reassessment of Phe tolerance may be necessary in adults [42]. Although Phe tolerance is a good indicator for the PKU phenotype, its determination may be unreliable if not determined under standardized conditions.…”

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

207

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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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

207

168

View full text Add to dashboard Cite

show abstract

“…However, as described in the recent study of MacLeod et al [18], and also from our own experience, we know that prescribed Phe can be very different form real daily Phe allowance, especially in adults. Further research on the fate of ingested Phe is necessary to be able to give a more precise prediction of blood Phe concentration resulting from a certain Phe intake.…”

Section: Discussionmentioning

confidence: 55%

Adult Patients with Well-Controlled Phenylketonuria Tolerate Incidental Additional Intake of Phenylalanine

Rijn¹,

Hoeksma²,

Sauer³

et al. 2011

Ann Nutr Metab

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Background/Aims: In patients with phenylketonuria (PKU), target ranges of blood phenylalanine (Phe) concentrations have been tightened in order to improve long-term outcomes. We investigated day-to-day and week-to-week variations in blood Phe concentration and the effect of an additional Phe load. Methods: We performed a longitudinal study in 6 adult PKU patients. The study was divided in five 7-day periods: 1 period without any intervention (period I) and 4 periods with a Phe load on day 3 equivalent to 100% (periods II and III) and to 200% (periods IV and V) of each patient’s individual daily Phe intake. Phe loading was given as encapsulated L-Phe. Blood spots to measure blood Phe concentration were taken each morning before breakfast in all periods. Results: Day-to-day and week-to-week blood Phe concentrations varied considerably with and without intervention in Phe intake. Equal loads of Phe did not result in comparable effects in blood Phe concentrations in all patients. In periods II–IV, mean blood Phe concentrations of days 1–3 (pre-load) were not significantly different from days 4–7 (post-load). The 200% load resulted in a significantly larger variation. Conclusion: These results showed that patients with well-controlled PKU can incidentally tolerate 100% – and in some cases 200% – of their normal daily Phe intake.

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“…Further studies would therefore be welcomed on therapeutically relevant aspects like the possible influence of obesity on phe tolerance (MacLeod et al 2009), the degree of oxidative stress at elevated blood phe levels (Okano and Nagasaka 2013), the value of self-management in improving the patients' individual responsibility and adherence (ten Hoedt et al 2011), the development and production of more palatable and satiating low-phe food products (van Calcar and Ney 2012) and the practicality of home monitoring (Wendel and Langenbeck 1996). Progress in these fields would contribute to converting a cumbersome disease into an aspect of self-determined life, like diabetes mellitus.…”

Section: Discussionmentioning

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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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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Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes

Cited by 45 publications

References 37 publications

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

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

Adult Patients with Well-Controlled Phenylketonuria Tolerate Incidental Additional Intake of Phenylalanine

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

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