Article (Scientific journals)
Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: A new phenotype
Blau, N.; Bonafé, L.; Krägeloh-Mann, I. et al.
2003In Neurology, 61 (5), p. 642-647
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Keywords :
DNA; Aicardi Goutieres syndrome; DNA sequence; Basal Ganglia; Brain Diseases; Decalcification, Pathologic; DNA Mutational Analysis; Dyskinesias; Female; Fibroblasts; Folic Acid; Humans; Infant; Infant, Newborn; Intracellular Signaling Peptides and Proteins; Leucovorin; Male; Mental Retardation; Microcephaly; Muscle Hypertonia; Phenotype; Proteins; Psychomotor Disorders; Pterins; Seizures; Syndrome; Tomography, X-Ray Computed
Abstract :
[en] Objective: To describe three unrelated children with a distinctive variant of Aicardi-Goutières syndrome (AGS) characterized by microcephaly, severe mental and motor retardation, dyskinesia or spasticity, and occasional seizures. Results: Neuroimaging showed bilateral calcification of basal ganglia and white matter. CSF glucose, protein, cell count, and interferon alpha were normal. Abnormal CSF findings included extremely high neopterin (293 to 814 nmol/L; normal 12 to 30 nmol/L) and biopterin (226 to 416 nmol/L; normal 15 to 40 nmol/L) combined with lowered 5-methyltetrahydrofolate (23 to 48 nmol/L; normal 64 to 182 nmol/L) concentrations in two patients. The absence of pleocytosis and normal CSF interferon alpha was a characteristic finding compared to the classic AGS syndrome. Genetic and enzymatic tests excluded disorders of tetrahydrobiopterin metabolism, including mutation analysis of GTP cyclohydrolase feed-back regulatory protein. CSF investigations in three patients with classic AGS also showed increased pterins and partially lowered folate levels. Conclusions: Intrathecal overproduction of pterins is the first biochemical abnormality identified in patients with AGS variants. Long-term substitution with folinic acid (2-4 mg/kg/day) resulted in substantial clinical recovery with normalization of CSF folates and pterins in one patient and clinical improvement in another. The underlying defect remains unknown.
Disciplines :
Pediatrics
Neurology
Author, co-author :
Blau, N.;  Div. of Clin. Chem. and Biochemistry, University Children's Hospital, Zurich, Switzerland, Div. of Clin. Chem. and Biochemistry, University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland
Bonafé, L.;  CHU Vaudois Lausanne, Suisse > Molecular Pediatrics
Krägeloh-Mann, I.;  University Hospital Tübingen > Pediatric Neurology
Thöny, B.;  Div. of Clin. Chem. and Biochemistry, University Children's Hospital, Zurich, Switzerland
Kierat, L.;  Div. of Clin. Chem. and Biochemistry, University Children's Hospital, Zurich, Switzerland
Häusler, M.;  University Hospital Aachen, Germany > Pediatric Neurology
Ramaekers, Vincent ;  University Hospital Aachen, Germany > Pediatric Neurology
Language :
English
Title :
Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: A new phenotype
Publication date :
09 September 2003
Journal title :
Neurology
ISSN :
0028-3878
eISSN :
1526-632X
Publisher :
Lippincott Williams & Wilkins, United States - Maryland
Volume :
61
Issue :
5
Pages :
642-647
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 07 June 2014

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