Endocrine Abstracts

Introduction: Pycnodysostosis (PYCD) is a rare autosomal recessive disorder caused by a mutation in cathepsin K (CTSK) gene resulting in increased bone density. The condition is characterised by short stature, acro-osteolysis of distal phalanges, osteosclerosis with increased bone fragility, dysplastic clavicula, delayed closure of sutures, mandibular hypoplasia, dental crowding and upper airway obstruction, causing obstructive sleep apnoea syndrome (OSAS). We report a child treated with hematopoietic stem cell transplantation (HSCT).

Case report: A12-year-old born to consanguineous parents. Both older brothers with PYCD had significant growth failure, multiple fractures with poor union, and OSAS requiring tracheostomies in early childhood. Eldest brother’s final height (FH) was 129.9 cm (SDS: −6.06), and the second brother’s FH was 140.5 cm (SDS: −4.43). At birth, he had micrognathia, pansystolic heart murmur and inspiratory stridor. Skeletal survey showed widespread sclerosis. Echocardiography revealed a small outlet ventricular septal defect. He had pathogenic homozygous variants in the CTSK gene: c.830C>T (P.A277V). Due to the severe phenotype, he had a matched family donor stem cell transplant at 9 months of life. Unlike older siblings, he did not develop OSAS symptoms or suffer fragility fractures. He has mild phenotypic features with micrognathia, hypoplastic maxilla, dental crowding, short dystrophic fingernails, and toenails. He has flat-footed gait and generalised joint hypermobility with Beighton score of 7/9. His latest height is 1.35 meters (SDS: −2.2), and weight at 39.9 kg (SDS: −0.28). BMI is 21.89 kg/m² (SDS: 1.88). Polysomnogram revealed mild elevation of Apnoea–Hypopnoea Index (AHI) of 1.3 per hour (<1 per hour). Bone age (TW3) was 13.29 years at chronological age 12.36 years. He has radiological signs of acro-osteolysis of distal phalanges. His size-corrected bone mineral density assessed by Dual-energy X-ray absorptiometry was normal: Bone mineral apparent density (BMAD) of the femoral neck SDS: −1.4 and BMAD of lumbar spine SDS: −0.8.

Conclusion: At present, pycnodysostosis treatment is largely supportive and symptomatic management of complications. HSCT in our patient normalised his bone mineral density, improved the linear growth and he did not develop symptoms of OSAS. HSCT should be considered in severe phenotypes of pycnodysostosis as it may potentially attenuate the phenotype.