title: Tyrosine hydroxylase deficiency unresponsive to L-dopa treatment with unusual clinical and biochemical presentation.
abstract: Tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa-responsive dystonia, also known as Segawa disease. Clinical hallmarks comprise parkinsonian and other extrapyramidal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a characteristic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a patient meeting all diagnostic criteria, including a new homozygous mutation (926T > C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed every 4 days and unresponsive to dopa treatment. The CSF biochemical abnormalities were severe. Uncharacteristically, a strongly abnormal urinary catecholamine metabolite pattern was also consistently observed. The atypical presentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condition should no longer be considered as a treatable disorder per se.
authors.affiliation: Département de Pédiatrique, H pital Necker-Enfants Malades, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: DE Lonlay
authors.forename: M C
authors.initials: MC
authors.lastname: Nassogne
authors.forename: A H
authors.initials: AH
authors.lastname: van Gennip
authors.forename: A C
authors.initials: AC
authors.lastname: van Cruchten
authors.forename: T
authors.initials: T
authors.lastname: Billatte de Villemeur
authors.forename: M
authors.initials: M
authors.lastname: Cretz
authors.forename: C
authors.initials: C
authors.lastname: Stoll
authors.forename: J M
authors.initials: JM
authors.lastname: Launay
authors.forename: G C
authors.initials: GC
authors.lastname: Steenberger-Spante
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: N G
authors.initials: NG
authors.lastname: Abeling
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D002675:Child, Preschool; D015259:Dopamine Agents / Q000627:therapeutic use*; D004829:Epilepsy, Generalized / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D009123:Muscle Hypotonia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D017211:Treatment Failure; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency* / Q000235:genetics
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase