BSPED2012 Oral Communications Oral Communications 2 (10 abstracts)
Growth, GH–IGF1 status and response to r-hGH therapy in 3-M syndrome, related to mutation status
Faezeh Sakhinia 1 , Dan Hanson 1 , Philip Murray 1 , Jeremy Kirk 3 , Trevor Cole 3 , Mars Skae 2 , Indi Banerjee 2 , Raja Padidela 2 , Leena Patel 2 & Peter Clayton 1
1Endocrinology, University of Manchester, Manchester, UK; 2Royal Manchester Children’s Hospital, Manchester, UK; 3Birmingham Children’s Hospital, Birmingham, UK.
Background: 3-M syndrome is associated with severe proportionate pre- and postnatal growth restriction, and is caused by mutations in CUL7, OBSL1, or CCDC8 genes.
Aims and methods: To define baseline growth and GH–IGF1 axis status as well as response to r-hGH in relation to mutation status in 3-M children, using retrospective analysis of data from clinical notes.
Results: 50 individuals (19 CUL7, 19 OBSL1, and 12 CCDC8 mutations) were identified. The mean (range) birth weight SDS was −2.6 (−0.8 to −4) at a mean gestational age of 38 weeks. The mean (range) height SDS at presentation was −4.9 (−2.7 to −7.3), at a mean age of 4 years; those with CCDC8 mutations were taller than those with CUL7 (P=0.07) or OBSL1 (P=0.045) mutations (CCDC8, −3.8 SDS; OBSL1, −5 SDS; and CUL7, −5.4 SDS).
The mean peak GH to arginine stimulation was 13.3 μg/l (range 3.7 to 38.3, n=12) and mean IGF1 SDS was −1.6 (range +0.2 to −5, n=14)). Results were consistent with GH resistance (peak GH≥7 μg/l and IGF1 SDS ≤−2) in five.
Twenty had been treated with r-hGH therapy (with doses escalating over time from 24–74 μg/kg per day); mean height gains of +0.2 and +1.1 SDS were observed over one and 5 years of treatment respectively, but marked inter-individual variation was noted. IGF1 SDS increased to a mean of +2.2 in the 1st year despite a modest growth response, suggesting IGF1 resistance. A better response over 5 years was noted in those with a CCDC8 mutation (mean +1.7 SDS) compared to those with an OBSL1 mutation (mean +0.8 SDS).
Discussion: 3-M children respond less well to r-hGH than SGA children in general. Those with CCDC8 mutations have a milder growth phenotype and respond better to r-hGH. 3-M mutations appear to be associated with partial GH and IGF1 resistance.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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