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

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          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.

          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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          Most cited references 29

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          Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations.

          The aim of the Task Force was to derive continuous prediction equations and their lower limits of normal for spirometric indices, which are applicable globally. Over 160,000 data points from 72 centres in 33 countries were shared with the European Respiratory Society Global Lung Function Initiative. Eliminating data that could not be used (mostly missing ethnic group, some outliers) left 97,759 records of healthy nonsmokers (55.3% females) aged 2.5-95 yrs. Lung function data were collated and prediction equations derived using the LMS method, which allows simultaneous modelling of the mean (mu), the coefficient of variation (sigma) and skewness (lambda) of a distribution family. After discarding 23,572 records, mostly because they could not be combined with other ethnic or geographic groups, reference equations were derived for healthy individuals aged 3-95 yrs for Caucasians (n=57,395), African-Americans (n=3,545), and North (n=4,992) and South East Asians (n=8,255). Forced expiratory value in 1 s (FEV(1)) and forced vital capacity (FVC) between ethnic groups differed proportionally from that in Caucasians, such that FEV(1)/FVC remained virtually independent of ethnic group. For individuals not represented by these four groups, or of mixed ethnic origins, a composite equation taken as the average of the above equations is provided to facilitate interpretation until a more appropriate solution is developed. Spirometric prediction equations for the 3-95-age range are now available that include appropriate age-dependent lower limits of normal. They can be applied globally to different ethnic groups. Additional data from the Indian subcontinent and Arabic, Polynesian and Latin American countries, as well as Africa will further improve these equations in the future.
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            Fleischner Society: glossary of terms for thoracic imaging.

            Members of the Fleischner Society compiled a glossary of terms for thoracic imaging that replaces previous glossaries published in 1984 and 1996 for thoracic radiography and computed tomography (CT), respectively. The need to update the previous versions came from the recognition that new words have emerged, others have become obsolete, and the meaning of some terms has changed. Brief descriptions of some diseases are included, and pictorial examples (chest radiographs and CT scans) are provided for the majority of terms. (c) RSNA, 2008.
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              Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).

              Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. Forty-nine patients -- 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent -- were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication. Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age. The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults.

                Author and article information

                ++49 89 44005 7870 ,
                Orphanet J Rare Dis
                Orphanet J Rare Dis
                Orphanet Journal of Rare Diseases
                BioMed Central (London )
                27 March 2018
                27 March 2018
                : 13
                [1 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Ludwig-Maximilians University, Dr von Haunersches Kinderspital, German Center for Lung Research (DZL), ; Lindwurmstr. 4, 80337 Munich, Germany
                [2 ]ISNI 0000 0000 8584 9230, GRID grid.411067.5, University Hospital Gießen and Marburg, German Center for Lung Research, ; Feulgenstr. 12, 35385 Gießen, Germany
                [3 ]ISNI 0000 0001 2165 8627, GRID grid.8664.c, Department of Internal Medicine, , Justus-Liebig University, German Center for Lung Research, ; Klinikstrasse 36, 35392 Giessen, Germany
                [4 ]ISNI 0000 0004 0551 4246, GRID grid.16149.3b, University Hospital Münster, ; Albert-Schweitzer-Campus 1, 48149 Münster, Germany
                [5 ]ISNI 000000040459992X, GRID grid.5645.2, Erasmuc MC, , University Medical Center Rotterdam, ; S’Gravendijkwal 230, 3015 Rotterdam, The Netherlands
                [6 ]ISNI 0000 0004 0627 3560, GRID grid.52522.32, St.Olav’s University Hospital, ; Trondheim, Norway
                [7 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Klinikum Bielefeld Mitte, , Institut für Pathologie, ; Teutoburger Straße 50, 33604 Bielefeld, Germany
                [8 ]Member of the European IPF Network, Lung Clinic Waldhof-Elgershausen, Greifenstein, Germany
                [9 ]Ludwig-Maximilians University, Institute of Pathology, Thalkirchnerstr. 36, 80337 Munich, Germany
                [10 ]ISNI 0000 0004 1936 973X, GRID grid.5252.0, Department of Radiology, , Ludwig-Maximilians University, ; Lindwurmstr. 4, 80337 Munich, Germany
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, 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 ( applies to the data made available in this article, unless otherwise stated.

                Funded by: European Union’s Seventh Framework Program
                Award ID: 305653
                Award Recipient :
                Funded by: German Center for lung research (DZL)
                Funded by: German Center for lung research (DZL)
                Funded by: European Cooperation in Science and Technology ()
                Award ID: A16125
                Award Recipient :
                Funded by: Curetis, Holzgerlingen, Germany
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