title: 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.affiliation: Department of Pediatrics, BC's Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, Canada.
authors.forename: Gabriella A
authors.initials: GA
authors.lastname: Horvath
authors.forename: Sylvia G
authors.initials: SG
authors.lastname: Stockler-Ipsiroglu
authors.forename: Ramona
authors.initials: R
authors.lastname: Salvarinova-Zivkovic
authors.forename: Yolanda P
authors.initials: YP
authors.lastname: Lillquist
authors.forename: Mary
authors.initials: M
authors.lastname: Connolly
authors.forename: Keith
authors.initials: K
authors.lastname: Hyland
authors.forename: Nenad
authors.initials: N
authors.lastname: Blau
authors.forename: Tony
authors.initials: T
authors.lastname: Rupar
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Waters
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003677:Deficiency Diseases / Q000175:diagnosis; D004421:Dystonia / Q000235:genetics / Q000378:metabolism; D006136:GTP Cyclohydrolase / Q000172:deficiency* / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D010649:Phenylalanine / Q000097:blood*
chemical_list: D010649:Phenylalanine; D006136:GTP Cyclohydrolase