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Tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Dutch neonates

Spaapen, L. J.M. ; Bakker, J. A. ; Velter, C. ; Loots, W. ; Rubio-Gonzalbo, M. E. ; Forget, P. P. ; Dorland, L. ; De Koning, T. J. LU ; Poll-The, B. T. and Ploos Van Amstel, H. K. , et al. (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.

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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}},
}