Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts

Details

Serval ID
serval:BIB_43CC714D41DD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Diagnosis of dopa-responsive dystonia and other tetrahydrobiopterin disorders by the study of biopterin metabolism in fibroblasts
Journal
Clinical Chemistry
Author(s)
Bonafe  L., Thony  B., Leimbacher  W., Kierat  L., Blau  N.
ISSN
0009-9147
Publication state
Published
Issued date
03/2001
Peer-reviewed
Oui
Volume
47
Number
3
Pages
477-85
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
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.
Keywords
Alcohol Oxidoreductases/metabolism Biopterin/*analogs & derivatives/biosynthesis/*deficiency/metabolism Cell Extracts Cells, Cultured Cytokines/pharmacology Dihydropteridine Reductase/metabolism Dihydroxyphenylalanine/*therapeutic use Dopamine Agents/*therapeutic use Dystonia/*diagnosis/drug therapy Female Fibroblasts/cytology/enzymology/*metabolism GTP Cyclohydrolase/metabolism Humans Male Metabolism, Inborn Errors/*diagnosis Neopterin/biosynthesis Phosphorus-Oxygen Lyases/metabolism Reference Values Skin/cytology
Pubmed
Web of science
Create date
21/01/2008 12:50
Last modification date
20/08/2019 13:47
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