Clinical and biochemical characterization of patients with early infantile onset of autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia

• Verfasst von: Opladen, Thomas [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Hörster, Friederike [VerfasserIn]
• Verfasst von: Hinz, Anne-Bärbel [VerfasserIn]
• Verfasst von: Neidhardt, Katharina [VerfasserIn]
• Verfasst von: Klein, Christine [VerfasserIn]
• Verfasst von: Wolf, Nicole [VerfasserIn]
• Titel: Clinical and biochemical characterization of patients with early infantile onset of autosomal recessive GTP cyclohydrolase I deficiency without hyperphenylalaninemia
• Verf.angabe: Thomas Opladen, Georg Hoffmann, Friederike Hörster, Anne-Bärbel Hinz, Katharina Neidhardt, Christine Klein, and Nicole Wolf
• Jahr: 2011
• Umfang: 5 S.
• Fussnoten: First published online: 03 September 2010 ; Gesehen am 13.10.2022
• Titel Quelle: Enthalten in: Movement disorders
• Ort Quelle: New York, NY : Wiley, 1986
• Jahr Quelle: 2011
• Band/Heft Quelle: 26(2011), 1 vom: Jan., Seite 157-161
• ISSN Quelle: 1531-8257
• DOI: doi:10.1002/mds.23329
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: autosomal recessive GTP cyclohydrolase I
• Sach-SW: dopa-responsive dystonia
• Sach-SW: extrapyramidal movements
• Sach-SW: hyperphenylalaninemia
• Sach-SW: tetrahydrobiopterin
• Sach-SW: truncal hyptonia
• K10plus-PPN: 1818881438

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. © 2010 Movement Disorder Society