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

Meike Hengst,
Lutz Naehrlich,
Poornima Mahavadi,
Joerg Grosse-Onnebrink,
Suzanne Terheggen-Lagro,
Lars Høsøien Skanke,
Luise A. Schuch,
Frank Brasch,
Andreas Guenther,
Simone Reu,
Julia Ley-Zaporozhan† and
Matthias Griese†Email author View ORCID ID profile

†Contributed equally

Orphanet Journal of Rare Diseases201813:42

https://doi.org/10.1186/s13023-018-0780-z

Received: 13 November 2017

Accepted: 1 March 2018

Published: 27 March 2018

Abstract

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.