Early pulmonary phenotype in Hermansky-Pudlak syndrome: Analysis of the chILD-EU registry

Abstract

Background Hermansky-Pudlak Syndrome (HPS) is a rare hereditary multisystem disorder, characterized by oculocutaneous albinism, bleeding diathesis, pulmonary fibrosis, neutropenia and granulomatous colitis. Based on the responsible genes, nine types of HPS are known; among these types 1, 2, and 4 have been associated with pulmonary fibrosis. Aims and objectives Investigate the early pulmonary phenotype in infants and young children. Methods All patients categorized as HPS in the kids lung register were searched. Diagnosis was based on clinical symptoms and confirmed by genetics. Between 01/2001 and 02/2016 6 children were identified and analysed retrospectively. Results 5 children had HPS-2, 1 child HPS-1. Age at diagnosis ranged between 0.4 - 8.8 years (mean 2,7). There was a predominance of females (5/6), a relation not noted in literature. All children had at least one typical extrapulmonary sign of HPS. The girl with HPS-1 had no pulmonary symptoms, all children with HPS-2 had a pulmonary phenotype: recurrent pneumothoraces (3), dyspnoea (3), partial respiratory insufficiency (3), chronic cough (2). Chest CT was performed in all children with HPS-2, which showed ground glass opacity (3), honeycombing (2) and a reticular pattern (2). In a familial case one child died at the age of 6 years due to respiratory insufficiency. All others are alive. Conclusion Sporadic and familial cases with HPS can present in early infancy and may have a pulmonary phenotype which can determine the disease´s course. The treatment of life limiting respiratory diseases in children with HPS must be considered, e.g. when clinical trials on novel therapeutic interventions are performed for adults.