| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Articles |
1
Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland.
a Author for correspondence. Fax 41-1-266-7169; e-mail
Nenad.Blau{at}kispi.unizh.ch.
Background: Dopa-responsive dystonia (DRD) and tetrahydrobiopterin (BH4) defects are inherited disorders characterized by monoamine neurotransmitter deficiency with decreased activity of one of the BH4-metabolizing enzymes. The aim of the study was to determine the utility of cultured skin fibroblasts for the diagnosis of these diseases.
Methods: Neopterin and biopterin production and GTP cyclohydrolase I (GTPCH) activity were measured in cytokine-stimulated fibroblasts; 6-pyruvoyltetrahydropterin synthase (PTPS), sepiapterin reductase (SR), and dihydropteridine reductase (DHPR) activities were measured in unstimulated fibroblasts. We examined 8 patients with DRD, 3 with autosomal recessive GTPCH deficiency, 7 with PTPS deficiency, 3 with DHPR deficiency, and 49 controls (35 fibroblast and 14 amniocyte samples).
Results: Fibroblasts from patients with DRD and autosomal recessive GTPCH deficiency showed reduced GTPCH activity (15.4% and 30.7% of normal activity, respectively) compared with controls (P <0.001). Neopterin production was very low and biopterin production was reduced in both disorders. PTPS- and DHPR-deficient cells showed no enzyme activities; in PTPS deficiency the pattern of pterin production was typical (neopterin, 334–734 pmol/mg; controls, 18–98 pmol/mg; biopterin, 0 pmol/mg; controls, 154–303 pmol/mg). Reference values of all enzyme activities and pterin production were measured in fibroblasts and also in amniocytes for prenatal diagnosis.
Conclusions: Cultured skin fibroblasts are a useful tool in the diagnosis of BH4 deficiencies. Intracellular neopterin and biopterin concentrations and GTPCH activity in cytokine-stimulated fibroblasts are particularly helpful in diagnosing patients with DRD.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  M von Mering, H Gabriel, T Opladen, G F Hoffmann, and A Storch A novel mutation (c.64_65delGGinsAACC [p.G21fsX66]) in the GTP cyclohydrolase 1 gene that causes Segawa disease J. Neurol. Neurosurg. Psychiatry, February 1, 2008; 79(2): 229 - 229. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Widder, W. Chen, L. Li, S. Dikalov, B. Thony, K. Hatakeyama, and D. G. Harrison Regulation of Tetrahydrobiopterin Biosynthesis by Shear Stress Circ. Res., October 12, 2007; 101(8): 830 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hyland Inherited Disorders Affecting Dopamine and Serotonin: Critical Neurotransmitters Derived from Aromatic Amino Acids J. Nutr., June 1, 2007; 137(6): 1568S - 1572S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J L K Van Hove, J Steyaert, G Matthijs, E Legius, P Theys, R Wevers, A Romstad, L B Moller, K Hedrich, D Goriounov, et al. Expanded motor and psychiatric phenotype in autosomal dominant Segawa syndrome due to GTP cyclohydrolase deficiency J. Neurol. Neurosurg. Psychiatry, January 1, 2006; 77(1): 18 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Franscini, E. B. Bachli, N. Blau, M. Fischler, R. B. Walter, A. Schaffner, and G. Schoedon Functional Tetrahydrobiopterin Synthesis in Human Platelets Circulation, July 13, 2004; 110(2): 186 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Blau, L. Bonafe, I. Krageloh-Mann, B. Thony, L. Kierat, M. Hausler, and V. Ramaekers Cerebrospinal fluid pterins and folates in Aicardi-Goutieres syndrome: A new phenotype Neurology, September 9, 2003; 61(5): 642 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Elzaouk, W. Leimbacher, M. Turri, B. Ledermann, K. Burki, N. Blau, and B. Thony Dwarfism and Low Insulin-like Growth Factor-1 Due to Dopamine Depletion in Pts-/- Mice Rescued by Feeding Neurotransmitter Precursors and H4-biopterin J. Biol. Chem., July 18, 2003; 278(30): 28303 - 28311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nardocci, G. Zorzi, N. Blau, E. Fernandez Alvarez, M. Sesta, L. Angelini, M. Pannacci, F. Invernizzi, and B. Garavaglia Neonatal dopa-responsive extrapyramidal syndrome in twins with recessive GTPCH deficiency Neurology, January 28, 2003; 60(2): 335 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Nemeth The genetics of primary dystonias and related disorders Brain, April 1, 2002; 125(4): 695 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bonafe, N. Blau, A. P. Burlina, A. Romstad, F. Guttler, and A. B. Burlina Treatable neurotransmitter deficiency in mild phenylketonuria Neurology, September 11, 2001; 57(5): 908 - 911. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
