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Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience


Opladen, T; Abu Seda, B; Rassi, A; Thöny, B; Hoffmann, G F; Blau, N (2011). Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. Journal of Inherited Metabolic Disease, 34(3):819-826.

Abstract

In every newborn with even mild hyperphenylalaninemia (HPA) tetrahydrobiopterin (BH(4)) deficiencies need to be excluded as soon as possible. Differential diagnosis is most commonly performed by analysis of urinary neopterin and biopterin. In 2005 a new method for the measurement of neopterin, biopterin and other pterins in dried blood spot (DBS) on filter paper was introduced. In order to evaluate the usefulness of this method as a standard tool for differential diagnosis of HPAs we analyzed neopterin, biopterin, pterin and dihydropteridine reductase activity in DBS from 362 patients with HPA over the period of five years. Age-dependent reference values were established for the HPA population. Sixty-four patients with BH(4) deficiency (27 patients with 6-pyruvoyl-tetrahydropterin synthase deficiency, seven with GTP cyclohydrolase I deficiency, and 30 with dihydropteridine reductase) were identified. Reference values for neopterin and biopterin in DBS were calculated for each of the variants. 6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. Regarding test sensitivity, the interpretation of neopterin and biopterin concentration per hemoglobin is more valid than the interpretation of neopterin and biopterin per liter. Percentage of biopterin, of the sum of neopterin and biopterin should always be calculated. In addition, determination of hemoglobin concentration is essential as a measure for efficient extraction of neopterin and biopterin. Although the measurement of neopterin and biopterin in urine is more sensitive due to the higher concentrations present, our data prove the usefulness of their measurement from DBS for the routine diagnosis of BH(4) deficiencies.

In every newborn with even mild hyperphenylalaninemia (HPA) tetrahydrobiopterin (BH(4)) deficiencies need to be excluded as soon as possible. Differential diagnosis is most commonly performed by analysis of urinary neopterin and biopterin. In 2005 a new method for the measurement of neopterin, biopterin and other pterins in dried blood spot (DBS) on filter paper was introduced. In order to evaluate the usefulness of this method as a standard tool for differential diagnosis of HPAs we analyzed neopterin, biopterin, pterin and dihydropteridine reductase activity in DBS from 362 patients with HPA over the period of five years. Age-dependent reference values were established for the HPA population. Sixty-four patients with BH(4) deficiency (27 patients with 6-pyruvoyl-tetrahydropterin synthase deficiency, seven with GTP cyclohydrolase I deficiency, and 30 with dihydropteridine reductase) were identified. Reference values for neopterin and biopterin in DBS were calculated for each of the variants. 6-pyruvoyl-tetrahydropterin synthase and GTP cyclohydrolase I deficiency can be diagnosed by neopterin and biopterin analysis alone, while for diagnosis of dihydropteridine reductase deficiency additional determination of enzyme activity from the same DBS is essential. Regarding test sensitivity, the interpretation of neopterin and biopterin concentration per hemoglobin is more valid than the interpretation of neopterin and biopterin per liter. Percentage of biopterin, of the sum of neopterin and biopterin should always be calculated. In addition, determination of hemoglobin concentration is essential as a measure for efficient extraction of neopterin and biopterin. Although the measurement of neopterin and biopterin in urine is more sensitive due to the higher concentrations present, our data prove the usefulness of their measurement from DBS for the routine diagnosis of BH(4) deficiencies.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:14 Jul 2011 08:47
Last Modified:05 Apr 2016 14:57
Publisher:Springer
ISSN:0141-8955
Publisher DOI:10.1007/s10545-011-9300-1
PubMed ID:21416196
Permanent URL: http://doi.org/10.5167/uzh-48657

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