Hermansky–Pudlak Syndrome

Abstract

Hermansky–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.

A family history of Hermansky–Pudlak syndrome complicated with pulmonary fibrosis: a case series and review

“…PF associated with HPS should be suspected in albino patients with bleeding, progressive dyspnoea, a restrictive airflow pattern in pulmonary function tests [2], and radiological findings consistent with ILD. Although several radiological patterns have been described, subpleural infiltrates, ground-glass reticular opacities, pleural thickening, and interstitial fibrosis, among others, can be highlighted [2,3,9].…”

“…Among the complementary tests useful to confirm the diagnosis, it is worth mentioning the study of platelets by electron microscopy, which allows confirming the reduced number or absence of platelet dense bodies [2]. Optionally, urine studies could also be performed to determine the presence of a ceroid-lipofuscin complex [10], or even the ceroid collection in the affected organs could be observed in autopsy studies [11].…”

“…Although rare, other organs can also be affected, the lung being the most frequent [1]. Albeit the real frequency of the syndrome is unknown, there are approximately 1200 cases worldwide [2,3]. This syndrome was first described at Czechoslovakia in 1959 [1]; however, more than 50% of the cases have been described in Puerto Rico or in Puerto Rican population [4].…”

“…HPS physiopathology consists of several mutations that affect the functions of some lysosomal-related organelles, such as melanosomes, the platelet dense bodies, and the lamellar bodies of type II pneumocytes [5][6][7][8]. Impairment of these organelles may explain some of these disease manifestations such as bleeding, albinism, and the far less likely pulmonary fibrosis (PF) [2,4,8].…”

Current strategies and opportunities to manufacture cells for modeling human lungs

“…In one study, Chen et al . developed LBOs (complex organoids with branching structures) to model pulmonary fibrosis associated with an autosomal recessive disorder called Hermansky-Pudlak syndrome (HPS) by deleting the HPS1 gene in their PSC line [ 158 , 159 ]. These LBOs demonstrated diminished branching, contained a high proportion of proliferative mesenchymal cells, and showed increased deposition of ECM proteins (collagen I, collagen III, and fibronectin), consistent with a fibrotic state [ 26 ].…”