title: n of 1 trial for an ornithine transcarbamylase deficiency carrier.
abstract: Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of the urea cycle. It is often fatal in affected males. Treatment for affected individuals includes dietary protein restriction, activation of alternative pathways of nitrogen excretion and L-arginine supplementation. Depending on the amount of X chromosome inactivation skewing, females show variable clinical manifestations, and sometimes the need for treatment, including medications, is unclear. We conducted an n of 1 randomized controlled trial on an obligate OTC carrier. The treating physician and patient were blinded to treatment. Either placebo capsules or L-arginine capsules were given for weekly periods. Weekly efficacy indicators included plasma arginine and glutamine levels and a quality of life/mood assessment questionnaire scale. Clear evidence of benefit with L-arginine compared to placebo was shown. This is the first time an n of 1 randomized controlled trial has been reported for an X-linked metabolic condition. Despite some logistic hurdles, we have demonstrated that this method was an effective tool for determining the value of treatment. We propose that other rare metabolic conditions may be amenable to such trials, if the benefit of treatment is in doubt.
authors.affiliation: Hunter Genetics, P.O. Box 84, Waratah, Newcastle, NSW 2298, Australia; University of Newcastle, NSW, Australia. anna.hackett@hnehealth.nsw.gov.au
authors.forename: A
authors.initials: A
authors.lastname: Hackett
authors.forename: J
authors.initials: J
authors.lastname: Gillard
authors.forename: B
authors.initials: B
authors.lastname: Wilcken
mesh_terms: D000339:Affect; D001120:Arginine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000188:drug therapy; D005973:Glutamine / Q000097:blood; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000188:drug therapy*; D011788:Quality of Life; D011795:Surveys and Questionnaires; D049951:X Chromosome Inactivation
chemical_list: D005973:Glutamine; D001120:Arginine; D009954:Ornithine Carbamoyltransferase