Assessment of tetrahydrobiopterin (BH4)-responsiveness and spontaneous phenylalanine reduction in a phenylalanine hydroxylase deficiency population

Tanšek, Mojca Žerjav; Grošelj, Urh; Murko, Simona; Kobe, Helena; Lampret, Barbka Repič; Battelino, Tadej

doi:10.1016/j.ymgme.2012.07.010

Cited by 14 publications

(16 citation statements)

References 53 publications

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“…6 It has been shown that genotypes are useful in predicting BH4 responsiveness in PKU patients. [7][8][9][10] The aim of PKU treatment is to maintain Phe blood concentrations within the therapeutic range, which is mainly achieved by a natural protein-restricted diet and synthetic amino acid supplementation without Phe. 11 However, the recommended low-Phe diet potentially impairs quality of life by decreasing patients' flexibility and autonomy.…”

Section: Discussionmentioning

confidence: 99%

Long-term Follow-up and Outcome of Phenylketonuria Patients on Sapropterin: A Retrospective Study

et al. 2013

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WHAT'S KNOWN ON THIS SUBJECT: Pharmacologic treatment with sapropterin dihydrochloride (6R-tetrahydrobiopterin; BH4) has been an effective option for some phenylketonuria patients since its approval by the US Food and Drug Administration in 2007 and the European Medicines Agency in 2008. WHAT THIS STUDY ADDS:This retrospective multicenter study revealed the long-term effects of sapropterin on metabolic control, dietary tolerance, and the outcome of BH4-responsive phenylketonuria patients harboring specific phenotypes and genotypes. It also confirmed that the minor adverse events disappeared by lowering the dose. abstract OBJECTIVE: Sapropterin dihydrochloride, the synthetic form of 6R-tetrahydrobiopterin (BH4), is an approved drug for the treatment of patients with BH4-responsive phenylketonuria (PKU). The purpose of this study was to assess genotypes and data on the long-term effects of BH4/sapropterin on metabolic control and patient-related outcomes in 6 large European countries. METHODS:A questionnaire was developed to assess phenotype, genotype, blood phenylalanine (Phe) levels, Phe tolerance, quality of life, mood changes, and adherence to diet in PKU patients from 16 medical centers. RESULTS:One hundred forty-seven patients, of whom 41.9% had mild hyperphenylalaninemia, 50.7% mild PKU, and 7.4% classic PKU, were followed up over #12 years. A total of 85 different genotypes were reported. With the exception of two splice variants, all of the most common mutations were reported to be associated with substantial residual Phe hydroxylase activity. Median Phe tolerance increased 3.9 times with BH4/sapropterin therapy, compared with dietary treatment, and median Phe blood concentrations were within the therapeutic range in all patients. Compared with diet alone, improvement in quality of life was reported in 49.6% of patients, improvement in adherence to diet was reported in 47% of patients, and improvement in adherence to treatment was reported in 63.3% of patients. No severe adverse events were reported. CONCLUSIONS: Our data document a long-term beneficial effect of orally administered BH4/sapropterin in responsive PKU patients by improving the metabolic control, increasing daily tolerance for dietary Phe intake, and for some, by improving dietary adherence and quality of life. Patient genotypes help in predicting BH4 responsiveness.

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Section: Discussionmentioning

confidence: 99%

Long-term Follow-up and Outcome of Phenylketonuria Patients on Sapropterin: A Retrospective Study

et al. 2013

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“…Blood spots were allowed to dry at room temperature for at least 4 h before the analysis. Blood samples were obtained on the occasion of ongoing long-term follow-up study of patients with mild HPA and of another study assessing BH4-responsiveness-the later cohort, protocol and results were described previously [19,20]. The samples were derived from altogether 51 patients, followed-up at our center.…”

Section: Blood Sample Collectionmentioning

confidence: 99%

Comparison of tandem mass spectrometry and amino acid analyzer for phenylalanine and tyrosine monitoring—Implications for clinical management of patients with hyperphenylalaninemia

Grošelj

Murko

Tanšek

et al. 2015

Clinical Biochemistry

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“…However QoL scores of PKU patients and their parents measured by current inventories are reported to be generally similar to healthy controls’ [ 14 , 17 , 18 ], probably as the questionnaires are not able to outline differences or criticalities expected in a chronic disease. Demirdas et al and Ziesch et al [ 14 , 16 ], for instance, investigated QoL of PKU patients using several instruments, before and after the introduction of BH 4 [ 19 ]. Their results showed that: QoL global scores were comparable to the ones of general population; QoL scores did not improve after BH 4 administration and consequential relaxation of diet.…”

Section: Introductionmentioning

confidence: 99%

Quality of Life (QoL) assessment in a cohort of patients with Phenylketonuria

Cazzorla¹,

Cegolon

Celato³

et al. 2014

BMC Public Health

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BackgroundPhenylketonuria (PKU) is a chronic inborn error of amino acid metabolism that requires lifelong follow-up and intervention, which may represent strains on Quality of Life (QoL). This observational study evaluated QoL in a cohort of PKU patients, using updated and detailed instruments.Methods22 patients with mild PKU respondent to BH4 and 21 patients with classical PKU treated with diet were recruited in this study. Adult patients completed WHOQOL questionnaire-100 (WHOQOL-100) and pediatric patients the Pediatric QoL inventory (PedsQLTM). Psychiatric and mood disorders were also evaluated using TAD or BDI and STAI-Y inventories. A multivariable linear regression model was fitted to investigate the predictors of QoL, including age, sex, treatment type, length of current treatment, educational level and employment status (only for adults) as covariates. Results were presented as regression coefficients with 95% confidence interval.ResultsGlobal QoL scores were within normal range both in patients with mild and classical disease but global QoL scores were significantly higher in patients with mild PKU under BH4 treatment as compared to those affected by classical disease who were under diet regimen. Furthermore, QoL significantly increased in long treated PKU patients. Among adult patients, QoL scores were significantly lower in males, in patients with lower education and in those employed or unemployed as compared to students (baseline).ConclusionsBoth diet and medical treatment based upon BH4 seem to be associated with higher QoL in the long run. However, patients with mild PKU can rely on BH4 to achieve a higher Phe tolerance and a better compliance to therapy due to diet relaxation/avoidance. Some specific categories of patients with a lower QoL should be investigated more in depth, engaging with those at risk of lower treatment compliance. The questionnaires employed in the present study seemed to be able to effectively detect criticalities in QoL assessment and represent an advance from previous inventories employed in the past.

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Assessment of tetrahydrobiopterin (BH4)-responsiveness and spontaneous phenylalanine reduction in a phenylalanine hydroxylase deficiency population

Cited by 14 publications

References 53 publications

Long-term Follow-up and Outcome of Phenylketonuria Patients on Sapropterin: A Retrospective Study

Long-term Follow-up and Outcome of Phenylketonuria Patients on Sapropterin: A Retrospective Study

Comparison of tandem mass spectrometry and amino acid analyzer for phenylalanine and tyrosine monitoring—Implications for clinical management of patients with hyperphenylalaninemia

Quality of Life (QoL) assessment in a cohort of patients with Phenylketonuria

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