title: Positive effects of an angiotensin II type 1 receptor antagonist in Camurati-Engelmann disease: a single case observation.
abstract: Camurati-Engelmann disease is characterized by hyperostosis of the long bones and the skull, muscle atrophy, severe limb pain, and progressive joint contractures in some patients. It is caused by heterozygous mutations in the transforming growth factor β1 (TGFβ1) believed to result in improper folding of the latency-associated peptide domain of TGFβ1 and thus in increased or deregulated bioactivity. Losartan, an angiotensin II type 1 receptor antagonist, has been found to downregulate the expression of TGFβ type 1 and 2 receptors. Clinical trials with losartan have shown a benefit in Marfan syndrome, while trials are underway for Duchenne muscular dystrophy and other myopathies associated with TGFβ1 signaling. We hypothesized that due to its anti-TGFβ1 activity, losartan might be beneficial in Camurati-Engelmann disease. This report concerns a boy who presented at age 13 years with severe limb pain and difficulty in walking. Clinical and radiographic evaluation results were compatible with Camurati-Engelmann disease and the diagnosis was confirmed by mutation analysis (c.652C > T [p.Arg218Cys]). The boy underwent an experimental treatment with losartan at a dosage of 50 mg/day, orally. During the treatment period of 18 months, the intensity and frequency of limb pain decreased significantly (as shown by a pain diary), and muscle strength improved, allowing the boy to resume walking and climbing stairs. No obvious side effects were observed. We cautiously conclude that TGFβ1 inhibition with losartan deserves further evaluation in the clinical management of Camurati-Engelmann disease.
authors.affiliation: Unit of Pediatric Genetics Department of Pediatrics, Hacettepe University Medical Faculty, Ankara, Turkey; Division of Molecular Pediatrics Department of Pediatrics, University of Lausanne, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Pelin Ozlem
authors.initials: PO
authors.lastname: Simsek-Kiper
authors.forename: Esra
authors.initials: E
authors.lastname: Dikoglu
authors.forename: Belinda
authors.initials: B
authors.lastname: Campos-Xavier
authors.forename: Gulen Eda
authors.initials: GE
authors.lastname: Utine
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafe
authors.forename: Sheila
authors.initials: S
authors.lastname: Unger
authors.forename: Koray
authors.initials: K
authors.lastname: Boduroglu
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
mesh_terms: D000293:Adolescent; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D003966:Camurati-Engelmann Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009154:Mutation / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan
keywords: Camurati-Engelmann disease; TGFβ1; losartan