- Oral presentation
- Open Access
Losartan improves clinical outcome in Camurati Engelmann Disease
International Journal of Pediatric Endocrinologyvolume 2013, Article number: O42 (2013)
We hypothesized that losartan would help in achieving clinical remission in CED (Camurati Engelmann Disease) patients by blocking TGFB1(transforming growth factor beta 1) with fewer side-effects than steroids.
CED characterised by progressive diaphyseal dysplasia is associated with debilitating bone pain in the limbs, muscle weakness, fatiguability and waddling gait. Clinical manifestations are due to mutations in the TGFB1 gene leading to its over-expression and effect on bone. Losartan is an antagonist of TGFB1 and it slows the progress of aortic root dilatation inMarfan’s syndrome by blocking the over-expression of TGFB1. Steroids which have long been used for treatment of CED and been linked to long term side effects including those on growth, blood pressure and spinal osteoporosis.
A 10 year old child with mutation is in exon 4, position C652T causing an R218C amino acid substitution on chromosome 19q13 had severe limitation of activity since 4 years of age due to pain in the limbs. She underwent a physical examination, a dual energy xray absorptiometry scan(DEXA), pain score and 6 minute walk test prior to the start of losartan with a repeat of the tests 9 and 17 months later. She is being treated with losartan at a dose of 0.75mg/kg/day. Table 1
Losartan improves the quality of life in children with CED by reducing the bone pain along with improvement in their activity levels, fat & muscle mass, without major effects on growth, blood pressure and spinal osteoporosis.
Janssens K, Vanhoenacker F, Bonduelle M, et al: Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment. Journal of Medical Genetics. 2006, 43: 1-
Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC: Angiotensin II blockade and aortic-root dilation in Marfan's syndrome. New England Journal of Medicine. 2008, 358: 2787-95. 10.1056/NEJMoa0706585.