Autosomal dominant GTP cyclohydrolase I deficiency

Autosomal dominant GTP cyclohydrolase I deficiency is a disease caused by dysfunction of GTP cyclohydrolase I, an enzyme needed to synthesize tetrahydrobiopterin and, through it, dopamine. It is one of six known causes of tetrahydrobiopterin deficiency and the most frequently reported cause of dopa-responsive dystonia. It results from mutations in the GCH1 gene. Onset is typically in the first decade of life, with postural or action-induced dystonia of one or both legs causing gait difficulty that worsens through the day and eases after rest. Unlike most tetrahydrobiopterin deficiencies it does not cause hyperphenylalaninemia, so newborn screening misses it, and diagnosis was delayed on average eight to ten years in data gathered by 2021.