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Beneficial Prenatal Levodopa Therapy in Autosomal Recessive Guanosine Triphosphate Cyclohydrolase 1 Deficiency

Norbert Brüggemann, MD; Juliane Spiegler, MD; Yorck Hellenbroich, MD; Thomas Opladen, MD; Susanne A. Schneider, MD, PhD; Ulrich Stephani, MD; Rainer Boor, MD; Gabriele Gillessen-Kaesbach, MD; Jürgen Sperner, MD; Christine Klein, MD
Arch Neurol. 2012;69(8):1071-1075. doi:10.1001/archneurol.2012.104.
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Objective  To report the first prenatal dopaminergic replacement therapy in autosomal recessive (AR) guanosine triphosphate cyclohydrolase 1 (GTPCH) deficiency without hyperphenylalaninemia.

Design  Case reports, literature review, and video presentation.

Setting  University of Lübeck, Lübeck, Germany.

Patients  Two boys from a consanguineous family.

Main Outcome Measures  Physical and mental development as a function of replacement initiation.

Results  The older sibling presented with typical features of AR GTPCH deficiency due to a homozygous mutation in the GCH1 gene with proven pathogenicity. Levodopa treatment was initiated at age 10 months and resulted in a distinct motor improvement. However, mental development was delayed. In the younger sibling, prenatal replacement therapy was initiated after a prenatal diagnosis of AR GTPCH deficiency was made. At age 17 months, both motor and mental development were normal for his age.

Conclusions  This report highlights the importance of an early diagnosis, including prenatal diagnosis, of complex dopa-responsive extrapyramidal syndromes. Prenatally initiated dopaminergic replacement therapy is beneficial and thus justified in AR GTPCH deficiency, allowing prevention of significant impairment of mental abilities.

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Grahic Jump Location

Figure. Pedigree of the family. Solid symbols represent affected individuals; open symbols, unaffected family members; and dots, confirmed asymptomatic carriers of a single GCH1 mutation.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

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