Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia – effect on median Phe/Tyr ratios
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Mojca Zerjav Tansek
Abstract
Background: Phenylalanine hydroxylase deficiency causes various degrees of hyperphenylalaninemia (HPA). Tetrahydrobiopterin (BH4; sapropterin) reduces phenylalanine (Phe) levels in responders, enabling relaxation of dietary therapy. We aimed to assess long-term effects of BH4 treatment in HPA patients.
Methods: Nine pre-pubertal BH4 responsive children were treated with BH4 for at least 2 years. The median dietary tolerance to Phe and levels of blood Phe, tyrosine (Tyr), zinc, selenium and vitamin B12 and anthropometric measurements, in the 2 years periods before and after the introduction of BH4 treatment were analyzed and compared. Adverse effects of BH4 were assessed.
Results: The daily Phe tolerance had tripled, from pretreatment median value of 620 mg (IQR 400–700 mg) to 2000 (IQR 1000–2000 mg) after 2 years of follow up (p<0.001). The median blood Phe levels during the 2 years period before introducing BH4 did not change significantly during the 2 years on therapy (from 200 μmol/L; IQR 191–302 to 190 μmol/L; IQR 135–285 μmol/L), but the median blood Phe/Tyr ratio had lowered significantly from pre-treatment value 4.7 to 2.4 during the 2 years on therapy (p=0.01). Median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change while on BH4 therapy (p=NS). No adverse effects were noticed.
Conclusions: BH4 therapy enabled patients much higher dietary Phe intakes, with no noticeable adverse effects. Median blood Phe and Tyr levels, median zinc, selenium, vitamin B12 levels and anthropometric measurements did not change significantly on BH4 therapy, but median Phe/Tyr ratios had lowered.
Acknowledgments
We thank all the patients and parents for their kind participation in our study. We also thank Dr. Simona Murko for analytical laboratory work and the nursing team caring for the patients included.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The study was supported in part by the Slovenian National Research Agency grants J3-2412, J3-9663 and P3-0343.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2016 by De Gruyter
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Articles in the same Issue
- Frontmatter
- Review
- Resistance to thyroid hormone α, revelation of basic study to clinical consequences
- Original Articles
- Improved molecular diagnosis of patients with neonatal diabetes using a combined next-generation sequencing and MS-MLPA approach
- Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes
- Waist-to-height ratio as a marker of low-grade inflammation in obese children and adolescents
- Classification and clinical characterization of metabolically “healthy” obese children and adolescents
- Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia – effect on median Phe/Tyr ratios
- Compound heterozygous mutations (p.T561M and c.2422delT) in the TPO gene associated with congenital hypothyroidism
- Prevalence and clinical features of polycystic ovarian syndrome in adolescents with previous childhood growth hormone deficiency
- Urate crystals deposition in the feet of overweight juveniles and those with symptomatic hyperuricemia: a dual-energy CT study
- A novel ALMS1 homozygous mutation in two Turkish brothers with Alström syndrome
- Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family
- Pituitary gigantism: a retrospective case series
- Case Reports
- A novel OTX2 gene frameshift mutation in a child with microphthalmia, ectopic pituitary and growth hormone deficiency
- A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome
- A 33-year-old male patient with paternal derived duplication of 14q11.2–14q22.1~22.3: clinical course, phenotypic and genotypic findings
- Familial Turner syndrome: the importance of information
- De novo mutation of PHEX in a type 1 diabetes patient
- Congenital hypothyroidism and thyroid dyshormonogenesis: a case report of siblings with a newly identified mutation in thyroperoxidase
