Background: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce. Methods: Six children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded. Results: Pulmonary symptoms including dyspnea, coughing, need for oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean age of 8.83 years (range 2-15). All children had recurrent pulmonary infections, 3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of pulmonary complaints increased over time. The leading radiographic pattern was ground-glass opacities with a rapid increase in reticular pattern and traction bronchiectasis between initial and follow-up Computer tomography (CT) in all subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the patients received a lung biopsy for diagnosis; histological patterns were cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like, and desquamative interstitial pneumonia. Conclusions: HPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required.

Additional Metadata
Keywords Childhood, Hermansky-Pudlak syndrome type 2, Pulmonary fibrosis, Pulmonary phenotype, Tachydyspnea
Persistent URL dx.doi.org/10.1186/s13023-018-0780-z, hdl.handle.net/1765/105804
Journal Orphanet journal of rare diseases
Citation
Hengst, M. (Meike), Naehrlich, L. (Lutz), Mahavadi, P, Grosse-Onnebrink, J. (Joerg), Terheggen-Lagro, S. (Suzanne), Skanke, L.Hø. (Lars Høsøien), … Griese, M. (Matthias). (2018). Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood. Orphanet journal of rare diseases, 13(1). doi:10.1186/s13023-018-0780-z