A rare diagnosis: Hermansky-Pudlak syndrome in a patient with pulmonary fibrosis, oculocutaneous albinism and thrombocytopathy

2019 ◽  
Author(s):  
Martina Doubková ◽  
Jakub Trizuljak ◽  
Anna Hrazdirová ◽  
Zuzana Vrzalová ◽  
Ivona Blaháková ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Oculocutaneous Albinism ◽  
Hermansky Pudlak Syndrome ◽  
Rare Diagnosis

scholarly journals Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Pamela Velázquez-Díaz ◽  
Erika Nakajima ◽  
Parand Sorkhdini ◽  
Ashley Hernandez-Gutierrez ◽  
Adam Eberle ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Oculocutaneous Albinism ◽  
Alveolar Epithelial Cells ◽  
Multisystem Disorder ◽  
Alveolar Epithelial ◽  
Novel Treatments ◽  
Molecular Approaches ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

scholarly journals Hermansky–Pudlak syndrome pulmonary fibrosis: a rare inherited interstitial lung disease

2021 ◽  
Vol 30 (159) ◽  
pp. 200193
Author(s):  
Tadafumi Yokoyama ◽  
Bernadette R. Gochuico
Keyword(s):  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Lung Disease ◽  
Genetic Diseases ◽  
Autosomal Recessive Disorder ◽  
Oculocutaneous Albinism ◽  
Excessive Bleeding ◽  
Lung Physiology ◽  
Hermansky Pudlak Syndrome ◽  
Fibrotic Lung Disease

Pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a poor prognosis. Studying genetic diseases associated with pulmonary fibrosis provides insights into the pathogenesis of the disease. Hermansky–Pudlak syndrome (HPS), a rare autosomal recessive disorder characterised by abnormal biogenesis of lysosome-related organelles, manifests with oculocutaneous albinism and excessive bleeding of variable severity. Pulmonary fibrosis is highly prevalent in three out of 10 genetic types of HPS (HPS-1, HPS-2 and HPS-4). Thus, genotyping of individuals with HPS is clinically relevant. HPS-1 tends to affect Puerto Rican individuals due to a genetic founder effect. HPS pulmonary fibrosis shares some clinical features with idiopathic pulmonary fibrosis (IPF), including dyspnoea, cough, restrictive lung physiology and computed tomography (CT) findings of fibrosis. In contrast to IPF, HPS pulmonary fibrosis generally affects children (HPS-2) or middle-aged adults (HPS-1 or HPS-4) and may be associated with ground-glass opacification in CT scans. Histopathology of HPS pulmonary fibrosis, and not IPF, shows vacuolated hyperplastic type II cells with enlarged lamellar bodies and alveolar macrophages with lipofuscin-like deposits. Antifibrotic drugs approved as treatment for IPF are not approved for HPS pulmonary fibrosis. However, lung transplantation has been performed in patients with severe HPS pulmonary fibrosis. HPS pulmonary fibrosis serves as a model for studying fibrotic lung disease and fibrosis in general.

scholarly journals Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Martina Doubková ◽  
Jakub Trizuljak ◽  
Zuzana Vrzalová ◽  
Anna Hrazdirová ◽  
Ivona Blaháková ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Clinical Manifestation ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Oculocutaneous Albinism ◽  
Differential Diagnostics ◽  
Compound Heterozygous ◽  
Carrier Status ◽  
Whole Exome ◽  
Hermansky Pudlak Syndrome

Abstract Background Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous pathological variants in HPS1, HPS3, HPS4, and several other genes lead to clinical manifestation of the disease. Case presentation A 57-year-old female was admitted with congenital oculocutaneous albinism, thrombocytopathy and late-onset accelerated pulmonary fibrosis (first symptoms from age 50 onwards). Chest high-resolution computed tomography identified thickening of peribronchovascular interstitium, bronchiectasis, reticulations, honeycombing, ground glass opacities and lung parenchyma consolidations. HPS was clinically suspected. We performed whole exome sequencing (WES), a form of massive parallel sequencing, of proband-parents trio. Whole exome libraries were processed using KAPA Hyper Prep Kit, SeqCap EZ MedExome Enrichment Kit and HyperCap Bead Kit according to the SeqCap EZ HyperCap Workflow. The paired-end 2 × 75 bp sequencing was performed on the Illumina NextSeq 500 Sequencer (Illumina Inc., USA). Furthermore, obtained variants by WES were evaluated using a virtual panel of genes: HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN. We identified a compound heterozygous genotype in HPS1 gene in the proband. We identified a pathogenic frameshift variant c.1189delC; p.(Gln397Serfs*2), resulting in a premature stop codon. This variant has been previously associated with HPS. Furthermore, we characterized previously undescribed nonsense variant c.1507C > T; p.(Gln503*), resulting in a premature stop codon and mRNA degradation through nonsense-mediated decay. Sanger sequencing validated the presence of both variants and simultaneously confirmed the heterozygous carrier status of parents. Unfortunately, the patient died due to fulminant progression of pulmonary fibrosis 2 months after diagnostics. Conclusions Compound heterozygous mutations in HPS1 in the proband lead to disruption of HPS1 gene and clinical manifestation of HPS with severe pulmonary fibrosis. This case illustrates the need to consider HPS in differential diagnostics of pulmonary fibrosis. Pulmonary fibrosis is a common cause of death in HPS patients. Earlier diagnosis may enable better treatment for these patients.

scholarly journals Hermansky-Pudlak syndrome with a novel genetic variant in HPS1 and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases

Thorax ◽  
2018 ◽  
Vol 73 (11) ◽  
pp. 1085-1088 ◽  
Author(s):  
Oliver J McElvaney ◽  
Marjan Huizing ◽  
William A Gahl ◽  
Paul O’Donovan ◽  
Deirdre Horan ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Genetic Diseases ◽  
Oculocutaneous Albinism ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Autosomal Recessive Disorders ◽  
Dental Procedures ◽  
Hermansky Pudlak Syndrome ◽  
Biallelic Mutations ◽  
Recessive Disorders

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the HPS1 gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in HPS1. In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.

scholarly journals PIRFENIDONE FOR TREATMENT OF PULMONARY FIBROSIS IN HERMANSKY-PUDLAK SYNDROME-1

CHEST Journal ◽  
2008 ◽  
Vol 134 (4) ◽  
pp. 127P
Author(s):  
Bernadette R. Gochuico ◽  
Thomas C. Markello ◽  
Kevin J. O'Brien ◽  
Hilda Cardona ◽  
Jose Salas ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Hermansky Pudlak Syndrome

A Rare Case of Hermansky-Pudlak Syndrome Involving Bilateral Lung: Histopathologic and Electron Microscopic Findings

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S42-S43
Author(s):  
Atreyee Basu ◽  
Surya Seshan ◽  
Luis Angel ◽  
Andre Moreira ◽  
Fang Zhou
Keyword(s):  
Alveolar Macrophages ◽  
Lamellar Body ◽  
Oculocutaneous Albinism ◽  
Electron Microscopic ◽  
Restrictive Lung Disease ◽  
Breath Sounds ◽  
Membrane Bound ◽  
Hermansky Pudlak Syndrome ◽  
Bilateral Lung ◽  
End Stage

Abstract Introduction Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive hereditary disorder characterized by oculocutaneous albinism and bleeding diathesis. Transplantation is often conducted to treat lung fibrosis, which is the most fatal complication of this disease. While the literature discusses the diagnosis of HPS based on genetic testing, radiology, and electron microscopic (EM) findings of platelet granules, there is a paucity of images in the literature illustrating the pulmonary histopathologic and EM features of HPS. Case Report Here we present striking histopathologic and EM images from a case of pulmonary fibrosis due to HPS in a 48-year-old female. The patient presented with restrictive lung disease and bilateral decreased breath sounds with diffuse crackles. She was clinically diagnosed with HPS and underwent bilateral lung transplant. On histopathology, both pneumonectomy specimens showed diffuse interstitial fibrosing and cellular pneumonitis with end-stage remodeling and type II pneumocyte (PC-II) hyperplasia. The PC-IIs had abundant foamy cytoplasm and compressed scalloped nuclei. Alveolar macrophages contained fine brown granules positive for PAS-D stain. EM analysis revealed that the PC-IIs contained numerous lamellated myelin bodies (so-called giant lamellar body degeneration) suggestive of surfactant admixed with lipid and luminal microvilli. The pigmented alveolar macrophages also contained lamellated myelin bodies, as well as clusters of single membrane-bound structures with varying size and electron density admixed with vacuolar and granular debris suggestive of ceroid deposits. Conclusion Based on light microscopy, histochemical analysis, EM, and clinical presentation, it was concluded that our findings were consistent with pulmonary changes as seen in HPS.

Hermansky–Pudlak Syndrome

2020 ◽  
Vol 41 (02) ◽  
pp. 238-246
Author(s):  
Wilfredo De Jesus Rojas ◽  
Lisa R. Young
Keyword(s):  
Protein Trafficking ◽  
Health Management ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Oculocutaneous Albinism ◽  
Clinical Approach ◽  
Recessive Mutations ◽  
Hermansky Pudlak Syndrome ◽  
Traction Bronchiectasis

AbstractHermansky–Pudlak syndrome (HPS) is a multisystemic autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and lethal pulmonary fibrosis (PF) in some HPS subtypes. During middle adulthood, ground-glass opacities, reticulation, and traction bronchiectasis develop with progression of PF. HPS is an orphan disease occurring in 1 in 500,000 to 1,000,000 individuals worldwide, though the prevalence is 1 in 1,800 in individuals with Puerto Rican heritage. Recessive mutations or disruptions in HPS genes alter the function of HPS proteins which are components of biogenesis of lysosome-related organelle complexes and are critical for intracellular protein trafficking. Diagnosis and management of HPS-related comorbidities represent a challenge to physicians, and a multidisciplinary clinical approach is necessary for early detection, health management, and surveillance of PF in patients with HPS types 1, 2, and 4. Treatment options for individuals with HPS-PF include pirfenidone and lung transplantation. In this article, we describe the epidemiology, genetics, clinical manifestations, and management of HPS.

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