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Oral communications

Oral communications
  • Endocrinology and metabolism
  • Phenylketonuria (PKU)

Тип ресурса


Predicting BH4 responsive phenotypes

sara wettstein

It is possible to quantify the loss of stability in the PAH enzyme and predict BH4 responsiveness using genotype scoring, explained Ms Sarah Wettstein 1. This offers a robust method for patient characterization and management.

Prof Nenad Blau’s group set out to analyze data from locus-specific database PAHvdb (834 variants) and genotypes database BIOPKUdb (4181 patients with full genotype) at

The relative frequencies of mutations, genotypes, affected gene regions and protein domains were calculated. PAH mutations and genotypes were scored using four prediction tools. These scores were correlated with residual enzyme activity, patients’ phenotype, and BH4 response.

Ms Wettstein was awarded the prize for best oral communication at the symposium. She was presented with a voucher for €4,000 to fund her further participation in CME courses and congresses.

Sapropterin in Turkish children under four years old

serap sivri

Sapropterin is both safe and efficacious as a treatment for HPA in children under four-years-old, said Prof Serap Sivri 2, presenting recent work in Turkey. The BH4 loading test, along with molecular studies, is useful in the detection of responders but not always in the prediction of long-term responsiveness.

In the study (single center, cross-sectional) 44 patients (28 boys, 16 girls) were found to be responsive using a 48-hour BH4 loading test. Sapropterin treatment was for 12—45 months. Diet was liberalized in 25/30 (83.3%) of patients. Phe tolerance increased 2.26-fold (0.88-4.23) from a median of 47.5 mg/kg/day to a median of 114 mg/kg/day (p<0.001). Phe tolerance did not change significantly in 5 patients, so sapropterin was discontinued.

Effects of sapropterin treatment on blood prolactin and serotonin

danique vvan vliet

Recent work shows that BH4 at 20 mg/kg might improve neuropsychological functioning by increasing cerebral neurotransmitter synthesis in both BH4 responsive and unresponsive PKU patients, reported Dr Danique van Vliet 3. The effect seems irrespective of age, but may be dependent on:

  • dose
  • availability of adequate tyrosine (Tyr) and tryptophan (Trp)
  • Phe concentration (specifically the Phe:Tyr and/or Phe:Trp ratios.)

Reduced brain dopamine and serotonin concentrations have long been considered a contributory factor in the impaired neuropsychological functioning seen in PKU patients. It has been suggested that BH4, also a cofactor for Tyr and Trp hydroxylase, could also have a role in improving brain neurotransmitter synthesis beyond its effect through lowering Phe concentrations.

Hyperphenylalaninemia causes cholinergic alterations in rat brain


Phe induces cholinergic alterations in rat brains, said Ms Patrícia Fernanda Schuck 4. Since cholinergic imbalance is associated with progressive neurologic decline in learning and memory functions it is possible that acetylcholinesterase (AChE) alterations might contribute to the intellectual deficiency observed in HPA patients. Ms Schuck presented results from ongoing work to investigate the in vitro, in vivo and in silico effects of Phe on AChE activity and its expression.

Ms Schuck has been awarded the 2014 PKU Academy Fellowship to assist the continuation of this work.

Microcephaly and hyperphenylalaninemias

serap sivri

Screening for maternal PKU and mild hyperphenylalaninemia (MHP) is essential if the offspring has early-onset microcephaly not attributable to PKU, said Prof Serap Sivri 5. This is especially the case in a country, such as Turkey, where there is a high incidence of the disease but relatively late adoption of national screening.

BH4 responsiveness

ucar kalkan

Prof Uçar Kalkan6 reported the efficacy of BH4 treatment in terms of increased Phe tolerance in patients treated at the Ege University (İzmir, Turkey.) BH4 administration in HPA increased phenylalanine tolerance in BH4 responsive patients.


1 - Ms Sarah Wettstein (c/o Prof Nenad Blau, Division of Metabolism, University Children’s Hospital, Zürich, Switzerland)

2 - Prof Serap Sivri (Department of Pediatrics, Section of Metabolism, Faculty of Medicine, Hacettepe University Hospital, Ankara, Turkey)

3 - Dr Danique van Vliet (Division of Metabolic Diseases, University Medical Centre Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands)

4 - Ms Patrícia Fernanda Schuck (Laboratory for the Inborn Errors of Metabolism, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, Santa Caterina, Brazil)

5 - Prof Serap Sivri (Department of Pediatrics, Section of Metabolism, Faculty of Medicine, Hacettepe University Hospital, Ankara, Turkey)

6 - Prof Uçar Kalkan (Pediatric Metabolism Department, Ege University Medical Faculty, İzmir, Turkey)

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