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Title: Sepiapterin reductase deficiency : a treatable mimic of cerebral palsy
Authors: Friedman, Jennifer
Roze, Emmanuel
Abdenur, Jose E.
Chang, Richard
Gasperini, Serena
Saletti, Veronica
Wali, Gurusidheshwar M.
Eiroa, Hernan
Neville, Brian G. R.
Felice, Alex E.
Parascandalo, Raymond
Zafeiriou, Dimitrios I.
Arrabal-Fernandez, Luisa
Dill, Patricia
Eichler, Florian S.
Echenne, Bernard
Gutierrez-Solana, Luis G.
Hoffmann, Georg F.
Hyland, Keith
Kusmierska, Katarzyna
Tijssen, Marina A. J.
Lutz, Thomas
Mazzuca, Michel
Penzien, Johann
Poll-The, Bweetien Tien T.
Sykut-Cegielska, Jolanta
Szymanska, Krystyna
Thony, Beat
Blau, Nenad
Keywords: Cerebral palsy
Issue Date: 2012
Publisher: Wiley Online Library
Citation: Friedman, J., Roze, E., Abdenur, J. E., Chang, R., Gasperini, S., Saletti, V.,...Blau, N. (2012). Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Annals of Neurology, 71(4), 520-530.
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. Interpretation: 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.
Description: We thank Dr F. Clot for molecular and Dr T. Bottiglieri for biochemical analyses, and Dr M. Natowicz for commenting on the manuscript.
Appears in Collections:Scholarly Works - FacM&SPB

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