Pierson Diane M, Ionescu Diana, Qing Gefei, Yonan Abdullah M, Parkinson Kent, Colby Thomas C, Leslie Kevin
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Respiration. 2006;73(3):382-95. doi: 10.1159/000091609. Epub 2006 Feb 14.
Hermansky-Pudlak syndrome (HPS) is a rare heterogeneously inherited autosomal recessive group of disorders presenting with oculocutaneous albinism, bleeding diathesis and pulmonary disease. HPS is thought to occur as a consequence of disturbed formation or trafficking of intracellular vesicles, most importantly, melanosomes, platelet dense granules and lysosomes. The latter finding, in particular, contributes much to the morbidity associated with the disease, as ceroid lipofuscin deposits in lysosomes affect many organ systems. This is especially problematic in the lungs where it is often associated with pulmonary fibrosis and premature death. Currently, there are 7 known HPS genes in humans. In the mouse, at least 16 known HPS genes produce HPS-mutant phenotypes. The HPS gene mutation is considered to be one of the most prevalent single-gene disorders in northwest Puerto Rico, home to the largest cohort of known patients. In HPS, interventions addressing the bleeding diathesis and pulmonary fibrosis are often disappointingly ineffectual. Pirfenidone, a novel compound with documented anti-inflammatory, antioxidant and antifibrotic effects, appears to hold promise in delaying or preventing fibrosis. To date, there has been one successful lung transplant performed on a patient with HPS. We present a patient with HPS and review the current literature on our understanding of this rare disorder.
Hermansky-Pudlak综合征(HPS)是一组罕见的常染色体隐性遗传性疾病,其特征为眼皮肤白化病、出血倾向和肺部疾病。HPS被认为是由于细胞内囊泡,尤其是黑素小体、血小板致密颗粒和溶酶体的形成或运输受到干扰所致。后一发现尤其导致了与该疾病相关的发病率,因为溶酶体中的类蜡样脂褐质沉积会影响多个器官系统。这在肺部尤其成问题,因为它常与肺纤维化和过早死亡相关。目前,人类已知有7个HPS基因。在小鼠中,至少有16个已知的HPS基因会产生HPS突变表型。HPS基因突变被认为是波多黎各西北部最常见的单基因疾病之一,那里是已知患者数量最多的群体所在地。在HPS中,针对出血倾向和肺纤维化的干预措施往往效果不佳,令人失望。吡非尼酮是一种具有抗炎、抗氧化和抗纤维化作用的新型化合物,似乎有望延缓或预防纤维化。迄今为止,已有一例HPS患者成功接受了肺移植。我们报告一例HPS患者,并综述目前关于这种罕见疾病的认识的文献。