Heterozygous pathogenic variation in GCH1 associated with treatable severe spastic tetraplegia

Abstract

GCH1 encodes for GTP cyclohydrolase I and has been historically associated with two disorders: bi-allelic variations to tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia B (MIM #233910), while heterozygous variations cause autosomal dominant dopa-responsive dystonia (DRD). GCH1 pathogenic variations have also been described in Parkinson's disease and are known to have incomplete penetrance. More recently, three reports associated hereditary spastic paraplegia (HSP) with a rare heterozygous variant in GCH1, the same variants being often associated with DRD [1–3].