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

Orphanet J Rare Dis. 2018 Mar 27;13(1):42. doi: 10.1186/s13023-018-0780-z.


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.

Keywords: Childhood; Hermansky-Pudlak syndrome type 2; Pulmonary fibrosis; Pulmonary phenotype; Tachydyspnea.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Hermanski-Pudlak Syndrome / pathology*
  • Humans
  • Lung / pathology*
  • Male
  • Pulmonary Fibrosis / pathology*
  • Young Adult

Supplementary concepts

  • Hermansky Pudlak syndrome 2