Cerebrospinal fluid pterins and folates in Aicardi-Goutieres syndrome: a new phenotype

Details

Serval ID
serval:BIB_5A343DC2A525
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Cerebrospinal fluid pterins and folates in Aicardi-Goutieres syndrome: a new phenotype
Journal
Neurology
Author(s)
Blau  N., Bonafe  L., Krageloh-Mann  I., Thony  B., Kierat  L., Hausler  M., Ramaekers  V.
ISSN
1526-632X
Publication state
Published
Issued date
09/2003
Peer-reviewed
Oui
Volume
61
Number
5
Pages
642-7
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 9
Abstract
OBJECTIVE: To describe three unrelated children with a distinctive variant of Aicardi-Goutieres 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.
Keywords
Basal Ganglia/pathology Brain Diseases/*cerebrospinal fluid/diagnosis/enzymology DNA Mutational Analysis Decalcification, Pathologic/diagnosis Dyskinesias/diagnosis Female Fibroblasts/enzymology Folic Acid/*cerebrospinal fluid Humans Infant Infant, Newborn Intracellular Signaling Peptides and Proteins Leucovorin/therapeutic use Male Mental Retardation/diagnosis Microcephaly/diagnosis Muscle Hypertonia/diagnosis Phenotype Proteins/genetics Psychomotor Disorders/diagnosis Pterins/*cerebrospinal fluid/metabolism Seizures/diagnosis Syndrome Tomography, X-Ray Computed
Pubmed
Web of science
Create date
21/01/2008 13:50
Last modification date
20/08/2019 15:13
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