Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: Evidence of a phenotypic continuum between dominant and recessive forms

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• 作者：Gabriella A. Horvath ; Sylvia G. Stockler-Ipsiroglu ; Ramona Salvarinova-Zivkovic ; Yol ; a P. Lillquist ; Mary Connolly ; Keith Hyl ; Nenad Blau ; Tony Rupar ; Paula J. Waters
• 关键词：GTP cyclohydrolase I ; GCH1 ; Tetrahydrobiopterin ; BH₄ ; Hyperphenylalaninemia ; Neurotransmitters ; Dopa-responsive dystonia ; Extrapyramidal movements ; Oculogyric crises ; Limb spasticity
• 刊名：Molecular Genetics and Metabolism
• 出版年：2008
• 出版时间：May 2008
• 年：2008
• 卷：94
• 期：1
• 页码：127-131
• 全文大小：118 K

文摘

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.