Literature DB >> 20668943

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

Thomas Opladen1, Jürgen G Okun, Peter Burgard, Nenad Blau, Georg F Hoffmann.   

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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Year:  2010        PMID: 20668943     DOI: 10.1007/s10545-010-9164-9

Source DB:  PubMed          Journal:  J Inherit Metab Dis        ISSN: 0141-8955            Impact factor:   4.982


  13 in total

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Journal:  Clin Biochem       Date:  2006-04-19       Impact factor: 3.281

2.  Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts.

Authors:  L Bonafé; B Thöny; W Leimbacher; L Kierat; N Blau
Journal:  Clin Chem       Date:  2001-03       Impact factor: 8.327

3.  Screening for tetrahydrobiopterin deficiencies using dried blood spots on filter paper.

Authors:  Marcel R Zurflüh; Marcello Giovannini; Laura Fiori; Betina Fiege; Yasemin Gokdemir; Tolunay Baykal; Lucja Kierat; Konrad H Gärtner; Beat Thöny; Nenad Blau
Journal:  Mol Genet Metab       Date:  2005-11-07       Impact factor: 4.797

Review 4.  Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency.

Authors:  N Blau; L Bonafé; B Thöny
Journal:  Mol Genet Metab       Date:  2001 Sep-Oct       Impact factor: 4.797

Review 5.  Dopa-responsive dystonia. Delineation of the clinical syndrome and clues to pathogenesis.

Authors:  T G Nygaard
Journal:  Adv Neurol       Date:  1993

6.  Oral phenylalanine loading in dopa-responsive dystonia: a possible diagnostic test.

Authors:  K Hyland; J S Fryburg; W G Wilson; E M Bebin; L A Arnold; R S Gunasekera; R D Jacobson; E Rost-Ruffner; J M Trugman
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8.  Phenocopies in a large GCH1 mutation positive family with dopa responsive dystonia: confusing the picture?

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9.  Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.

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10.  Dopa-responsive dystonia: a clinical and molecular genetic study.

Authors:  O Bandmann; E M Valente; P Holmans; R A Surtees; J H Walters; R A Wevers; C D Marsden; N W Wood
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Journal:  JIMD Rep       Date:  2012-04-18

Review 2.  Recognizing Atypical Dopa-Responsive Dystonia and Its Mimics.

Authors:  Philippe A Salles; Mérida Terán-Jimenez; Alvaro Vidal-Santoro; Pedro Chaná-Cuevas; Marcelo Kauffman; Alberto J Espay
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3.  Recessive GCH1 Deficiency Causing DOPA-Responsive Dystonia Diagnosed by Reported Negative Exome.

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Journal:  Pediatrics       Date:  2022-02-01       Impact factor: 7.124

Review 4.  Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies.

Authors:  Thomas Opladen; Eduardo López-Laso; Elisenda Cortès-Saladelafont; Toni S Pearson; H Serap Sivri; Yilmaz Yildiz; Birgit Assmann; Manju A Kurian; Vincenzo Leuzzi; Simon Heales; Simon Pope; Francesco Porta; Angeles García-Cazorla; Tomáš Honzík; Roser Pons; Luc Regal; Helly Goez; Rafael Artuch; Georg F Hoffmann; Gabriella Horvath; Beat Thöny; Sabine Scholl-Bürgi; Alberto Burlina; Marcel M Verbeek; Mario Mastrangelo; Jennifer Friedman; Tessa Wassenberg; Kathrin Jeltsch; Jan Kulhánek; Oya Kuseyri Hübschmann
Journal:  Orphanet J Rare Dis       Date:  2020-05-26       Impact factor: 4.123

5.  Dopa-responsive dystonia in a ten-year-old girl.

Authors:  Venkatesh Soma; Hussain Sadiq Mohammed; Ebrahim Riyas; Karuppasamy Murugesan
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