title: Suppression of bilirubin production in the Crigler-Najjar type I syndrome: studies with the heme oxygenase inhibitor tin-mesoporphyrin.
abstract: The heme oxygenase inhibitor tin-mesoporphyrin was used to moderate hyperbilirubinemia in two 17-year-old boys with Crigler-Najjar type I syndrome. Both patients had histories of recent, progressive neurological deterioration and plasma bilirubin concentrations on admission to the hospital were 34.5 and 28.5 mg/dL. Throughout hospitalization lasting more than 400 days, both patients underwent 10 hours of phototherapy nightly and consumed constant weight-maintaining diets. They were treated with intermittent plasmapheresis and two periods of tin-mesoporphyrin therapy comprising, in the first study period, 40 doses of 0.5 mumol/kg body weight and in the second study period, 70 doses of 1.0 mumol/kg body weight. Plasma bilirubin concentrations were decreased in both patients to varying degrees as was the rebound hyperbilirubinemia which occurs after plasmapheresis. The prolonged treatments with the inhibitor were well-tolerated and no progression of the preexisting neurological impairments occurred during the clinical trials. The results of this study suggest that the clinical application of an effective heme oxygenase inhibitor can provide a potentially useful, pharmacological adjunct to presently available therapeutic modalities for controlling episodes of acute, severe jaundice in this but lethal disorder.
authors.affiliation: Rockefeller University Hospital, New York, NY 10021.
authors.forename: R A
authors.initials: RA
authors.lastname: Galbraith
authors.forename: G S
authors.initials: GS
authors.lastname: Drummond
authors.forename: A
authors.initials: A
authors.lastname: Kappas
mesh_terms: D000293:Adolescent; D001663:Bilirubin / Q000378:metabolism; D003131:Combined Modality Therapy; D003414:Crigler-Najjar Syndrome / Q000188:drug therapy* / Q000628:therapy; D004035:Diet Therapy; D004341:Drug Evaluation; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D010789:Phototherapy; D010956:Plasmapheresis; D013997:Time Factors
chemical_list: D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin