title: Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy.
abstract: OBJECTIVE
  Sepiapterin reductase deficiency (SRD) is an under-recognized levodopa-responsive disorder. We describe clinical, biochemical, and molecular findings in a cohort of patients with this treatable condition. We aim to improve awareness of the phenotype and available diagnostic and therapeutic strategies to reduce delayed diagnosis or misdiagnosis, optimize management, and improve understanding of pathophysiologic mechanisms.
  
  
  METHODS
  Forty-three individuals with SRD were identified from 23 international medical centers. The phenotype and treatment response were assessed by chart review using a detailed standardized instrument and by literature review for cases for which records were unavailable.
  
  
  RESULTS
  In most cases, motor and language delays, axial hypotonia, dystonia, weakness, oculogyric crises, and diurnal fluctuation of symptoms with sleep benefit become evident in infancy or childhood. Average age of onset is 7 months, with delay to diagnosis of 9.1 years. Misdiagnoses of cerebral palsy (CP) are common. Most patients benefit dramatically from levodopa/carbidopa, often with further improvement with the addition of 5-hydroxytryptophan. Cerebrospinal fluid findings are distinctive. Diagnosis is confirmed by mutation analysis and/or enzyme activity measurement in cultured fibroblasts.
  
  
  CONCLUSIONS
  Common, clinical findings of SRD, aside from oculogyric crises and diurnal fluctuation, are nonspecific and mimic CP with hypotonia or dystonia. Patients usually improve dramatically with treatment. Consequently, we recommend consideration of SRD not only in patients with levodopa-responsive motor disorders, but also in patients with developmental delays with axial hypotonia, and patients with unexplained or atypical presumed CP. Biochemical investigation of cerebrospinal fluid is the preferred method of initial investigation. Early diagnosis and treatment are recommended to prevent ongoing brain dysfunction.
authors.affiliation: Departments of Neurosciences and Pediatrics, University of California at San Diego and Rady Children's Hospital, USA. jrfriedman@rchsd.org
authors.forename: Jennifer
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authors.lastname: Friedman
authors.forename: Emmanuel
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authors.lastname: Roze
authors.forename: Jose E
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authors.forename: Richard
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authors.lastname: Gasperini
authors.forename: Veronica
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authors.forename: Alex
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authors.forename: Ray
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authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Zafeiriou
authors.forename: Luisa
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authors.lastname: Arrabal-Fernandez
authors.forename: Patricia
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authors.lastname: Dill
authors.forename: Florian S
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authors.lastname: Eichler
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authors.lastname: Kusmierska
authors.forename: Marina A J
authors.initials: MA
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authors.forename: Thomas
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authors.lastname: Lutz
authors.forename: Michel
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authors.lastname: Mazzuca
authors.forename: Johann
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authors.lastname: Penzien
authors.forename: Bwee Tien
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authors.lastname: Poll-The
authors.forename: Jolanta
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authors.lastname: Sykut-Cegielska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Szymanska
authors.forename: Beat
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authors.lastname: Thöny
authors.forename: Nenad
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authors.lastname: Blau
mesh_terms: D017668:Age of Onset; D000429:Alcohol Oxidoreductases / Q000172:deficiency* / Q000235:genetics*; D001483:Base Sequence; D002547:Cerebral Palsy / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D003937:Diagnosis, Differential; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009069:Movement Disorders / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D018377:Neurotransmitter Agents / Q000032:analysis / Q000627:therapeutic use
chemical_list: D015259:Dopamine Agents; D018377:Neurotransmitter Agents; D000429:Alcohol Oxidoreductases; C022630:sepiapterin reductase