ESPE Abstracts

Background: Pycnodysostosis is a very rare autosomal recessive skeletal dysplasia caused by cathepsin K deficiency. It is characterized by extreme short stature resulting in an adult height in males typically <150 cm and in females <134 cm. Bone-fragility and frequent fractures are present. There are few case-reports on the effects of GH treatment.

Objective: To evaluate the effect and safety of GH in 6 patients with pycnodysostosis treated according to the Dutch national pycnodysostosis guideline.

Patients: 6 subjects (4 boys, 2 girls) with pycnodysostosis, treated for ≥1 year with GH (~1.4 mg/m2/day). Endocrine evaluation before start of GH was normal.

Results: Median (IQR) age at start of GH was 10.4 years (5.3; 12.1) and median height 113.5 cm (97.1; 129.3) (Table 1). All children were prepubertal at start of GH. After 1 year of GH, median height gain was 8.0 cm (6.4; 8.5). Three subjects, relatively old at start of GH, reached adult height. Subject 4 (treated for 4.8 years) reached a height of 138.0 cm. Subject 5, reached a height of 157.0 cm (treated for 6.3 years). Subject 6 reached a height of 148.0 cm after 6.4 years of GH and additional GnRH analogue, which is much higher than typically described in females. No SAE’s were reported. Fractures occurred in 3 subjects. Frequency of fractures did not increase during GH treatment. Serum IGF-I remained below +2 SDS.

Conclusion: Pycnodysostosis is an extremely rare disorder and it is, therefore, impossible to perform a randomized control trial to evaluate the efficacy and safety of GH. Our data suggest that GH can prevent the decline in height SDS which is observed in children with pycnodysostosis. Further research is needed to confirm this. Also, the effect of other growth promoting strategies such as treatment with a GnRH analogue needs to be investigated.