Journal
MOLECULAR GENETICS AND METABOLISM
Volume 94, Issue 1, Pages 127-131Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2008.01.003
Keywords
GTP cyclohydrolase I; GCH1; tetrahydrobiopterin; BH4; hyperphenylalaninemia; neurotransmitters; dopa-responsive dystonia; extrapyramidal movements; oculogyric crises; limb spasticity
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We describe a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia. A male infant presented with progressive spasticity, dystonia, and oculogyric episodes. Blood phenylalanine levels were persistently normal: whereas an oral phenylalanine loading test revealed impaired phenylalanine clearance. CSF neopterin and tetrahydrobiopterin (BH4) Were low, homovanillic acid marginally low and 5-hydroxyindoleacetic acid normal. Fibroblasts showed decreased GTPCH enzyme activity. A homozygous novel mutation of GCH1, p.V206A, was identified. On treatment (BH4, L-Dopa/Carbidopa and 5-hydroxytryptophan), motor development improved. Mutational analysis provided neonatal diagnosis of a younger brother who, after 18 months on treatment, shows normal development. AR GTPCH I deficiency can present without hyperphenylalaninemia and with normal or subtle CSF neurotransmitter profiles. Testing for GTPCH deficiency should be considered for patients with unexplained neurological symptoms and extrapyramidal movement disorder. (c) 2008 Elsevier Inc. All rights reserved.
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