Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

Orphanet Journal of Rare Diseases - 2018
Meike Hengst1, Lutz Naehrlich2, Poornima Mahavadi3, Joerg Grosse-Onnebrink4, Suzanne Terheggen-Lagro5, Lars Høsøien Skanke6, Luise A. Schuch1, Frank Brasch7, Andreas Guenther3,8, Simone Reu9, Julia Ley-Zaporozhan10, Matthias Griese1
1Ludwig-Maximilians University, Dr von Haunersches Kinderspital, German Center for Lung Research (DZL), Munich, Germany
2University Hospital Gießen and Marburg, German Center for Lung Research, Gießen, Germany
3Department of Internal Medicine, Justus-Liebig University, German Center for Lung Research, Giessen, Germany
4University Hospital Münster, Münster, Germany
5Erasmuc MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
6St.Olav’s University Hospital, Trondheim, Norway
7Klinikum Bielefeld Mitte, Institut für Pathologie, Bielefeld, Germany
8Member of the European IPF Network, Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany
9Ludwig-Maximilians University, Institute of Pathology, Munich, Germany
10Department of Radiology, Ludwig-Maximilians-University, Munich, Germany

Tóm tắt

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. 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. 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. HPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required.

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