title: Pitfalls in phenylalanine loading test in the diagnosis of dopa-responsive dystonia.
abstract: Phenylalanine (Phe) loading test is a useful tool in the differential diagnosis of dopa-responsive dystonia due to autosomal dominant or recessive GTP cyclohydrolase I (GTPCH) deficiency or autosomal recessive sepiapterin reductase (SR) deficiency. In these patients hepatic phenylalanine hydroxylase system is compromised due to subnormal tetrahydrobiopterin (BH(4)) levels and hydroxylation of phenylalanine (Phe) to tyrosine (Tyr) is reduced with elevated Phe/Tyr ratio 1-2 h after oral Phe administration (100 mg/kg bw) administration. In healthy persons there is only a modest increase in Tyr production and blood Phe normalizes after 4 h. We report on a challenge with Phe (100 mg/kg bw) in a patient with dopa-responsive dystonia while on therapy with BH(4) and l-dopa. During Phe challenge Phe concentration remained below the normal range while a transient mild hypertyrosinemia was observed, leading to an extremely low Phe/Tyr ratio. A repeated test, after BH(4) withdrawal, reversed the findings and resulted normal. These data suggest activation of hepatic phenylalanine hydroxylase by BH(4). Thus, the Phe loading test should not be performed during substitution with BH(4).
authors: Division of Inborn Metabolic Diseases, University Children's Hospital, Heidelberg, Germany.
authors: Thomas
authors: T
authors: Opladen
authors: Georg F
authors: GF
authors: Hoffmann
authors: Andrea A
authors: AA
authors: Kühn
authors: Nenad
authors: N
authors: Blau
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D003937:Diagnosis, Differential; D004421:Dystonia / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D020821:Dystonic Disorders / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D010649:Phenylalanine / Q000008:administration & dosage* / Q000097:blood; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D011596:Psychomotor Disorders / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D014443:Tyrosine / Q000097:blood
chemical_list: D001708:Biopterins; D014443:Tyrosine; D007980:Levodopa; D010649:Phenylalanine; D010651:Phenylalanine Hydroxylase; C003402:sapropterin