Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates
(2001) In Journal of Inherited Metabolic Disease 24(3). p.352-358- Abstract
Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 μmol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH 4) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH 4 loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH 4 load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of... (More)
Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 μmol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH 4) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH 4 loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH 4 load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of control values in patient 4 (not in the range of DHPR-deficient patients). In patient 3 a subsequent phenylalanine loading test with concomitant analysis of plasma biopterins revealed a normal increase of biopterin, excluding a BH 4 biosynthesis defect. Pterins and neurotransmitter metabolites in CSF of patients 1, 3 and 4 were normal. DNA mutations detected in the PAH gene of patients 1-4 were A313T, and L367fsinsC; V190A and R243X; A300S and A403V; R241C and A403V. The results are suggestive for mutant PAH enzymes with decreased affinity for the cofactor BH 4.
(Less)
- author
- publishing date
- 2001-08-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Inherited Metabolic Disease
- volume
- 24
- issue
- 3
- pages
- 7 pages
- publisher
- Springer
- external identifiers
-
- pmid:11486900
- scopus:0034923705
- ISSN
- 0141-8955
- DOI
- 10.1023/A:1010596317296
- language
- English
- LU publication?
- no
- id
- f50815fc-c774-432a-86ca-7d6dc7f5c219
- date added to LUP
- 2020-03-03 19:12:06
- date last changed
- 2024-01-02 07:02:56
@article{f50815fc-c774-432a-86ca-7d6dc7f5c219, abstract = {{<p>Four neonates with a positive phenylalanine screening test (Phe concentrations between 258 and 1250 μmol/L) were investigated further to differentiate between phenylalanine hydroxylase (PAH) deficiency and variant hyperphenylalaninaemia (HPA) forms. In patients 1 and 2 a tetrahydrobiopterin (BH <sub>4</sub>) load caused a significant decrease of the plasma Phe levels. A combined phenylalanine/BH <sub>4</sub> loading test was performed in patients 2, 3 and 4. In the latter two patients, plasma Phe concentrations completely normalized within 8 h after the BH <sub>4</sub> load (20 mg/kg). Basal urinary pterins were normal in all four patients. The activity of dihydropteridine reductase (DHPR) was normal in patients 1, 2 and 3 and 50% of control values in patient 4 (not in the range of DHPR-deficient patients). In patient 3 a subsequent phenylalanine loading test with concomitant analysis of plasma biopterins revealed a normal increase of biopterin, excluding a BH <sub>4</sub> biosynthesis defect. Pterins and neurotransmitter metabolites in CSF of patients 1, 3 and 4 were normal. DNA mutations detected in the PAH gene of patients 1-4 were A313T, and L367fsinsC; V190A and R243X; A300S and A403V; R241C and A403V. The results are suggestive for mutant PAH enzymes with decreased affinity for the cofactor BH <sub>4</sub>.</p>}}, author = {{Spaapen, L. J.M. and Bakker, J. A. and Velter, C. and Loots, W. and Rubio-Gonzalbo, M. E. and Forget, P. P. and Dorland, L. and De Koning, T. J. and Poll-The, B. T. and Ploos Van Amstel, H. K. and Bekhof, J. and Blau, N. and Duran, M.}}, issn = {{0141-8955}}, language = {{eng}}, month = {{08}}, number = {{3}}, pages = {{352--358}}, publisher = {{Springer}}, series = {{Journal of Inherited Metabolic Disease}}, title = {{Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates}}, url = {{http://dx.doi.org/10.1023/A:1010596317296}}, doi = {{10.1023/A:1010596317296}}, volume = {{24}}, year = {{2001}}, }