Autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia: evidence of a phenotypic continuum between dominant and recessive forms.
|
| Abstract |
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 (BH(4)) 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 (BH(4), 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.
|
|---|---|
| Authors | Gabriella A Horvath, Sylvia G Stockler-Ipsiroglu, Ramona Salvarinova-Zivkovic, Yolanda P Lillquist, Mary Connolly, Keith Hyland, Nenad Blau, Tony Rupar, Paula J Waters |
| Journal | Molecular genetics and metabolism (Mol Genet Metab) Vol. 94 Issue 1 Pg. 127-31 (May 2008) ISSN: 1096-7206 [Electronic] United States |
| PMID | 18276179 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!