title: Clinical and biochemical characterization of patients with early infantile onset of autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia.
abstract: Autosomal recessive guanosine triphosphate cyclohydrolase (GTPCH) type I deficiency is characterized by complex neurological dysfunction. Patients are usually diagnosed with hyperphenylalaninemia in newborn screening. We describe two unrelated patients without hyperphenylalaninemia who presented during early infancy with severe motor retardation, hypokinesia, and truncal hypotonia. CSF homovanillic acid and 5-hydroxyindoleacetic acid as well as tetrahydrobiopterin and neopterin were decreased. Diagnosis of recessive GTPCH deficiency was confirmed biochemically, and a novel homozygous mutation was identified in one patient and a compound-heterozygous mutation of GCH1 in the other. Treatment with Levodopa/Carbidopa resulted in striking clinical improvement, with age-appropriate development at follow-up at 6 years. Autosomal recessive GTPCH deficiency should be considered in infants with severe truncal hypotonia even if hyperphenylalaninemia or classical extrapyramidal symptoms are missing. Neurotransmitter analysis followed by enzyme or mutation analysis can confirm the diagnosis, and Levodopa treatment should be started at high-doses.
authors.affiliation: University Children's Hospital Heidelberg, Division of Inborn Metabolic Diseases, Heidelberg, Germany. thomas.opladen@med.uni-heidelberg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Opladen
authors.forename: Georg
authors.initials: G
authors.lastname: Hoffmann
authors.forename: Friederike
authors.initials: F
authors.lastname: Hörster
authors.forename: Anne-Bärbel
authors.initials: AB
authors.lastname: Hinz
authors.forename: Katharina
authors.initials: K
authors.lastname: Neidhardt
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolf
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use; D002675:Child, Preschool; D003677:Deficiency Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006136:GTP Cyclohydrolase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D009154:Mutation / Q000235:genetics; D018377:Neurotransmitter Agents / Q000378:metabolism; D010661:Phenylketonurias / Q000503:physiopathology*
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D018377:Neurotransmitter Agents; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D006136:GTP Cyclohydrolase; D002230:Carbidopa