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

Gabriella A Horvath; Sylvia G Stockler-Ipsiroglu; Ramona Salvarinova-Zivkovic; Yolanda P Lillquist; Mary Connolly; Keith Hyland; Nenad Blau; Tony Rupar; Paula J Waters

doi:10.1016/j.ymgme.2008.01.003

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

Mol Genet Metab. 2008 May;94(1):127-31. doi: 10.1016/j.ymgme.2008.01.003. Epub 2008 Feb 13.

Authors

Gabriella A Horvath¹, Sylvia G Stockler-Ipsiroglu, Ramona Salvarinova-Zivkovic, Yolanda P Lillquist, Mary Connolly, Keith Hyland, Nenad Blau, Tony Rupar, Paula J Waters

Affiliation

¹ Department of Pediatrics, BC's Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC, Canada.

PMID: 18276179
DOI: 10.1016/j.ymgme.2008.01.003

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.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Child, Preschool
Consanguinity
DNA Mutational Analysis
Deficiency Diseases / diagnosis
Dystonia / genetics
Dystonia / metabolism
GTP Cyclohydrolase / deficiency*
GTP Cyclohydrolase / genetics*
Genes, Dominant*
Genes, Recessive*
Humans
Male
Mutation
Phenotype
Phenylalanine / blood*

Substances

Phenylalanine
GTP Cyclohydrolase