Supplementary Material for: Effects and safety of growth hormone treatment in six children with pycnodysostosis

Background: Pycnodysostosis is an extremely rare skeletal dysplasia caused by cathepsin K deficiency. It is characterized by extreme short stature with adult height in males typically less than 150 cm and in females less than 130 cm. Our objective was to evaluate the effect and safety of growth hormone (GH) treatment in 6 patients with pycnodysostosis treated according to the Dutch national pycnodysostosis guideline.
Case presentation: 6 subjects (4 boys, 2 girls) with pycnodysostosis, treated with GH 1.4 mg/m2/day (~0.046 mg/kg/day) for ≥1 year. Median (IQR) age at start of GH was 10.4 years (5.7; 12.2) and median height 113.5 cm (93.3; 129.3) (-4.2 SDS (-4.8; -3.6)). All children were prepubertal at start of GH. After 1 year of GH, median height gain was 7.6 cm (6.5; 8.5) (0.3 SDS (-0.3; 0.7)). Three children are still treated with GH and the other three subjects reached adult height (AH): 1 boy reached an AH of 157.0 cm (-3.8 SDS) after 6.3 years of GH, 2 girls reached an AH of 138.5 cm (-5.2 SDS) after 4.8 years of GH and 148.0 cm (-3.6 SDS) after 6.4 years of GH, respectively. This last girl received additional GnRH analogue treatment. In all subjects height SDS remained stable or improved during and after GH treatment. No serious adverse advents were found. Serum IGF-I remained below the +2 SDS.
Conclusion: Our data suggest that GH may prevent the decline in height which can be observed in children with pycnodysostosis. Further research is needed to confirm this. Also, the effect of other growth promoting strategies such as treatment with an additional GnRH analogue warrants further investigation.