The classic form of Ehlers-Danlos syndrome (cEDS) is an inherited connective 
tissue disorder, where mutations in type V collagen-encoding genes result in 
abnormal collagen fibrils. Thus the cEDS patients have pathological connective 
tissue morphology and low stiffness, but the rate of connective tissue protein 
turnover is unknown. We investigated whether cEDS affected the protein synthesis 
rate in skin and tendon, and whether this could be stimulated in tendon tissue 
with insulin-like growth factor-I (IGF-I). Five patients with cEDS and 10 
healthy, matched controls (CTRL) were included. One patellar tendon of each 
participant was injected with 0.1 ml IGF-I (Increlex, Ipsen, 10 mg/ml) and the 
contralateral tendon with 0.1 ml isotonic saline as control. The injections were 
performed at both 24 and 6 h prior to tissue sampling. The fractional synthesis 
rate (FSR) of proteins in skin and tendon was measured with the stable isotope 
technique using a flood-primed continuous infusion over 6 h. After the infusion 
one skin biopsy and two tendon biopsies (one from each patellar tendon) were 
obtained. We found similar baseline FSR values in skin and tendon in the cEDS 
patients and controls [skin: 0.005 ± 0.002 (cEDS) and 0.007 ± 0.002 (CTRL); 
tendon: 0.008 ± 0.001 (cEDS) and 0.009 ± 0.002 (CTRL) %/h, mean ± SE]. IGF-I 
injections significantly increased FSR values in cEDS patients but not in 
controls (delta values: cEDS 0.007 ± 0.002, CTRL 0.001 ± 0.001%/h). In 
conclusion, baseline protein synthesis rates in connective tissue appeared 
normal in cEDS patients, and the patients responded with an increased tendon 
protein synthesis rate to IGF-I injections.