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Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience.
J Inherit Metab Dis. 2011 Jun; 34(3):819-26.JI

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.

Authors+Show Affiliations

Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Heidelberg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21416196

Citation

Opladen, Thomas, et al. "Diagnosis of Tetrahydrobiopterin Deficiency Using Filter Paper Blood Spots: Further Development of the Method and 5 Years Experience." Journal of Inherited Metabolic Disease, vol. 34, no. 3, 2011, pp. 819-26.
Opladen T, Abu Seda B, Rassi A, et al. Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. J Inherit Metab Dis. 2011;34(3):819-26.
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), 819-26. https://doi.org/10.1007/s10545-011-9300-1
Opladen T, et al. Diagnosis of Tetrahydrobiopterin Deficiency Using Filter Paper Blood Spots: Further Development of the Method and 5 Years Experience. J Inherit Metab Dis. 2011;34(3):819-26. PubMed PMID: 21416196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diagnosis of tetrahydrobiopterin deficiency using filter paper blood spots: further development of the method and 5 years experience. AU - Opladen,Thomas, AU - Abu Seda,Bettina, AU - Rassi,Anahita, AU - Thöny,Beat, AU - Hoffmann,Georg F, AU - Blau,Nenad, Y1 - 2011/03/17/ PY - 2010/12/03/received PY - 2011/02/10/accepted PY - 2011/02/09/revised PY - 2011/3/19/entrez PY - 2011/3/19/pubmed PY - 2011/10/25/medline SP - 819 EP - 26 JF - Journal of inherited metabolic disease JO - J Inherit Metab Dis VL - 34 IS - 3 N2 - 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. SN - 1573-2665 UR - https://wwww.unboundmedicine.com/medline/citation/21416196/Diagnosis_of_tetrahydrobiopterin_deficiency_using_filter_paper_blood_spots:_further_development_of_the_method_and_5_years_experience_ L2 - https://doi.org/10.1007/s10545-011-9300-1 DB - PRIME DP - Unbound Medicine ER -