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

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 scar...

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Autores principales: Hengst, Meike, Naehrlich, Lutz, Mahavadi, Poornima, Grosse-Onnebrink, Joerg, Terheggen-Lagro, Suzanne, Skanke, Lars Høsøien, Schuch, Luise A., Brasch, Frank, Guenther, Andreas, Reu, Simone, Ley-Zaporozhan, Julia, Griese, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870397/
https://www.ncbi.nlm.nih.gov/pubmed/29580292
http://dx.doi.org/10.1186/s13023-018-0780-z
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author Hengst, Meike
Naehrlich, Lutz
Mahavadi, Poornima
Grosse-Onnebrink, Joerg
Terheggen-Lagro, Suzanne
Skanke, Lars Høsøien
Schuch, Luise A.
Brasch, Frank
Guenther, Andreas
Reu, Simone
Ley-Zaporozhan, Julia
Griese, Matthias
author_facet Hengst, Meike
Naehrlich, Lutz
Mahavadi, Poornima
Grosse-Onnebrink, Joerg
Terheggen-Lagro, Suzanne
Skanke, Lars Høsøien
Schuch, Luise A.
Brasch, Frank
Guenther, Andreas
Reu, Simone
Ley-Zaporozhan, Julia
Griese, Matthias
author_sort Hengst, Meike
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0780-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-58703972018-03-29 Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood Hengst, Meike Naehrlich, Lutz Mahavadi, Poornima Grosse-Onnebrink, Joerg Terheggen-Lagro, Suzanne Skanke, Lars Høsøien Schuch, Luise A. Brasch, Frank Guenther, Andreas Reu, Simone Ley-Zaporozhan, Julia Griese, Matthias Orphanet J Rare Dis Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13023-018-0780-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-27 /pmc/articles/PMC5870397/ /pubmed/29580292 http://dx.doi.org/10.1186/s13023-018-0780-z Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hengst, Meike
Naehrlich, Lutz
Mahavadi, Poornima
Grosse-Onnebrink, Joerg
Terheggen-Lagro, Suzanne
Skanke, Lars Høsøien
Schuch, Luise A.
Brasch, Frank
Guenther, Andreas
Reu, Simone
Ley-Zaporozhan, Julia
Griese, Matthias
Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title_full Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title_fullStr Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title_full_unstemmed Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title_short Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
title_sort hermansky-pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870397/
https://www.ncbi.nlm.nih.gov/pubmed/29580292
http://dx.doi.org/10.1186/s13023-018-0780-z
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