Autosomal dominant GTP cyclohydrolase I deficiency

[1] In more than half the cases, the clinical picture is dominated by postural or action-induced dystonia of one or both lower limbs manifesting as gait difficulties.

According to a consensus guideline on BH4 deficiency published in 2020, if the presence of AD-GTPCHD is suspected, a genetic assessment should be carried out to look for mutations of the GTPCH1 gene.

[2] Genetic assessment requires specialized methods able to detect deletions, because in a significant number of patients with AD-GTPCHD no sequence alterations were found.

[2] In children whose symptoms are suggestive of dopa-responsive dystonia but for whom neither genetic nor biochemical assessment are available, L-dopa could be briefly prescribed as a trial to see if the patient's condition improves.

[2] In case of improvement, the patient would be suspected to have autosomal dominant GTP cyclohydrolase I deficiency, but would still have to undergo genetic and biochemical testing to distinguish their condition from other diseases.

Figure 1. Pattern of cerebrospinal fluid markers in autosomal dominant GTP cyclohydrolase I deficiency compared with other forms of tetrahydrobiopterin deficiency , from a consensus guideline by Thomas Opladen et al., 2020. [ 2 ]