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Phenylalanine loading in pediatric patients with dopa-responsive dystonia: revised test protocol and pediatric cutoff values

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

An Erratum to this article was published on 10 September 2010

Abstract

Objectives

The objectives of this study were to determine the value of phenylalanine (Phe) loading for diagnosing dopa-responsive dystonia (DRD) in children.

Methods

We investigated orally administered Phe loading tests (100 mg/kg) in seven patients with confirmed DRD and 17 pediatric patients with clinically suspected but excluded DRD. Results of Phe, tyrosine (Tyr), and biopterin from plasma and dried blood spot (DBS) analyses were correlated, and pediatric cutoff values established.

Results

The peak Phe concentration following a Phe load in the pediatric DRD population is lower than reported in adults. By using adult cutoff values and either Phe/Try ratios or biopterin concentrations only, false positive and false negative results are frequent. Only the combined analysis of the Phe/Tyr ratio and biopterin concentration is reliable in children. In children with DRD, dried blood Phe/Tyr ratio exceeded 4.6 (plasma Phe/Tyr ratio >5.4) after 2 h and biopterin concentration in dried blood remained below 16.2 nmol/L (plasma biopterin <14 nmol/L) 1 h after Phe challenge.

Conclusions

Phe loading is a useful tool for diagnosing DRD in children. Test duration can be reduced to only 2 h, and specific pediatric cutoff values need to be applied. Simultaneous measurements of the Phe/Tyr ratio and biopterin in plasma or DBS are essential in pediatric patients.

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Acknowledgements

We thank Mrs. Brigitte Schmidt-Mader, Mr. Alexandros Anninos, and Mrs. Bettina Abu Seda for skilful technical assistance. This study was supported in part by the Swiss National Science Foundation grant no. 3100A0-119982/1 (to NB).

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Authors and Affiliations

  1. Division of Inherited Metabolic Diseases, University Children’s Hospital Heidelberg, Heidelberg, Germany

    Thomas Opladen, Jürgen G. Okun, Peter Burgard & Georg F. Hoffmann

  2. Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zürich, Zürich, Switzerland

    Nenad Blau

  3. Zürich Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland

    Nenad Blau

  4. Dept of General Pediatrics Division of Inherited Metabolic Diseases, University Children’s Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Thomas Opladen

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  1. Thomas Opladen
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  2. Jürgen G. Okun
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  3. Peter Burgard
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  4. Nenad Blau
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  5. Georg F. Hoffmann
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Corresponding author

Correspondence to Thomas Opladen.

Additional information

Communicated by: Jean-Marie Saudubray

Competing interest: None declared.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10545-010-9205-4

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Opladen, T., Okun, J.G., Burgard, P. et al. Phenylalanine loading in pediatric patients with dopa-responsive dystonia: revised test protocol and pediatric cutoff values. J Inherit Metab Dis 33, 697–703 (2010). https://doi.org/10.1007/s10545-010-9164-9

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  • DOI: https://doi.org/10.1007/s10545-010-9164-9

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