Tondi Francesca, Cirsmaru Roberta Annamaria, Conti Chiara, Follenzi Antonia, Gresele Paolo, Olgasi Cristina, Bury Loredana
Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Department of Health Sciences, School of Medicine, University of Piemonte Orientale, Novara, Italy.
IUBMB Life. 2025 May;77(5):e70025. doi: 10.1002/iub.70025.
Hermansky-Pudlak syndrome (HPS) is a rare inherited disorder caused by defects in lysosome-related organelles (LROs) in various tissues, including platelets, melanocytes, and endothelial cells. Key features of HPS include oculocutaneous albinism, bleeding tendency, and, in some cases, pulmonary fibrosis, granulomatous colitis, and immunodeficiency. The condition is linked to mutations in 11 genes involved in the formation of LROs. Currently, treatment options for HPS are limited and often ineffective. Though cell and gene therapies have been explored for melanosomes and epithelial cells, there is limited knowledge about their application to platelets and endothelial cells. Understanding the detailed mechanisms of HPS pathogenesis is crucial, and using induced pluripotent stem cell (iPSC) models may provide valuable insights into the disease's molecular processes, aiding the development of new treatments. In this review, we will focus on the genetics and molecular mechanisms of HPS, on its clinical manifestations and current therapeutic approaches, highlighting the need for further research into the disease mechanisms and potential innovative therapies.
赫尔曼斯基-普德拉克综合征（HPS）是一种罕见的遗传性疾病，由包括血小板、黑素细胞和内皮细胞在内的各种组织中的溶酶体相关细胞器（LRO）缺陷引起。HPS的主要特征包括眼皮肤白化病、出血倾向，在某些情况下还包括肺纤维化、肉芽肿性结肠炎和免疫缺陷。这种疾病与11个参与LRO形成的基因突变有关。目前，HPS的治疗选择有限且往往无效。尽管已经对黑素小体和上皮细胞进行了细胞和基因治疗的探索，但关于它们在血小板和内皮细胞中的应用知之甚少。了解HPS发病机制的详细机制至关重要，使用诱导多能干细胞（iPSC）模型可能会为该疾病的分子过程提供有价值的见解，有助于开发新的治疗方法。在这篇综述中，我们将重点关注HPS的遗传学和分子机制、其临床表现和当前的治疗方法，强调需要对疾病机制和潜在的创新疗法进行进一步研究。
