Autosomal Recessive Guanosine Triphosphate Cyclohydrolase (GTPCH) Deficiency
Although most mutations in guanosine triphosphate (GTP) cyclohydrolase to date have been documented in association with autosomal dominant dopa-responsive dystonia, or Segawa's disease, these patients do not have hyperphenylalaninemia on routine plasma screening studies. Patients with the autosomal recessive form of GTP cyclohydrolase deficiency, however, present in a similar fashion to patients with DHPR and PTS deficiency. Such patients have severe global developmental impairment, marked hypotonia of the trunk and axial muscles, eye movement abnormalities, limb hypertonia, convulsions, and autonomic symptoms including temperature dysregulation, excessive diaphoresis, and blood pressure lability caused by the associated catecholamine deficiency. They typically have absent GTP cyclohydrolase activity in blood cells, liver, and skin fibroblasts.
By contrast, patients with autosomal dominant dopa-responsive dystonia have preservation of some GTP cyclohydrolase activity in liver because of their heterozygous status, enough to maintain normal phenylalanine levels under usual circumstances. CSF neurotransmitter metabolite analysis reveals low levels of HVA and 5-HIAA, and low neopterin and biopterin levels.
