title: Levodopa-responsive infantile parkinsonism due to a novel mutation in the tyrosine hydroxylase gene and exacerbation by viral infections.
abstract: Autosomal recessive forms of infantile dystonia due to mutations in the tyrosine hydroxylase (TH) gene have been described recently. The main clinical manifestations are Segawa's disease, or infantile hypokinetic rigid Parkinsonism. Here, we report on a patient with hyperrigidity, psychomotor developmental delay, and dystonic posturing of the hands, symptoms that appeared after a viral infection at the age of 14 months. Low homovanillic acid/5-hydroxyindolacetic acid (HVA/5HIAA) ratio in cerebrospinal fluid suggested a TH deficiency. Molecular analysis revealed a novel (H246Y) and a known (D498G) compound heterozygote mutation in the TH gene. The patient showed a remarkable response to treatment with levodopa. The new mutation and the association of viral infections with the onset and worsening of symptoms are discussed.
authors.affiliation: Department of Pediatrics, Division of Neuropediatrics, University of Göttingen, 37099 Göttingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Diepold
authors.forename: Barbara
authors.initials: B
authors.lastname: Schütz
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Bernd
authors.initials: B
authors.lastname: Wilken
authors.forename: Pia
authors.initials: P
authors.lastname: Hougaard
authors.forename: Flemming
authors.initials: F
authors.lastname: Güttler
authors.forename: Anne
authors.initials: A
authors.lastname: Romstad
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Birk Møller
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D020805:Central Nervous System Viral Diseases; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006639:Histidine / Q000235:genetics; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007980:Levodopa / Q000627:therapeutic use*; D051379:Mice; D009154:Mutation; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D051381:Rats; D016896:Treatment Outcome; D014443:Tyrosine / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D014443:Tyrosine; D007980:Levodopa; D006639:Histidine; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D006719:Homovanillic Acid