Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy.
Medical Genetics Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, 20142 Milan, Italy.
Biomolecules. 2024 Feb 11;14(2):211. doi: 10.3390/biom14020211.
Niemann-Pick Disease (NPD) is a rare autosomal recessive disease belonging to lysosomal storage disorders. Three types of NPD have been described: NPD type A, B, and C. NPD type A and B are caused by mutations in the gene coding for sphingomyelin phosphodiesterase 1, with a consequent lack of acid sphingomyelinase activity. These diseases have been thus classified as acid sphingomyelinase deficiencies (ASMDs). NPD type C is a neurologic disorder due to mutations in the genes or , causing a defect of cholesterol trafficking and esterification. Although all three types of NPD can manifest with pulmonary involvement, lung disease occurs more frequently in NPD type B, typically with interstitial lung disease, recurrent pulmonary infections, and respiratory failure. In this sense, bronchoscopy with broncho-alveolar lavage or biopsy together with high-resolution computed tomography are fundamental diagnostic tools. Although several efforts have been made to find an effective therapy for NPD, to date, only limited therapeutic options are available. Enzyme replacement therapy with Olipudase α is the first and only approved disease-modifying therapy for patients with ASMD. A lung transplant and hematopoietic stem cell transplantation are also described for ASMD in the literature. The only approved disease-modifying therapy in NPD type C is miglustat, a substrate-reduction treatment. The aim of this review was to delineate a state of the art on the genetic basis and lung involvement in NPD, focusing on clinical manifestations, radiologic and histopathologic characteristics of the disease, and available therapeutic options, with a gaze on future therapeutic strategies.
尼曼-匹克病（Niemann-Pick Disease，NPD）是一种罕见的常染色体隐性遗传疾病，属于溶酶体贮积症。已经描述了三种类型的 NPD：NPD 型 A、B 和 C。NPD 型 A 和 B 是由编码鞘磷脂磷酸二酯酶 1 的基因突变引起的，导致酸性鞘磷脂酶活性缺乏。因此，这些疾病被归类为酸性鞘磷脂酶缺乏症（acid sphingomyelinase deficiencies，ASMDs）。NPD 型 C 是一种神经疾病，由于基因 或 中的突变，导致胆固醇转运和酯化缺陷。尽管所有三种类型的 NPD 都可能表现为肺部受累，但肺部疾病在 NPD 型 B 中更为常见，通常表现为间质性肺病、复发性肺部感染和呼吸衰竭。在这种情况下，支气管镜检查伴支气管肺泡灌洗或活检以及高分辨率计算机断层扫描是基本的诊断工具。尽管已经做出了许多努力来寻找有效的 NPD 治疗方法，但迄今为止，只有有限的治疗选择可用。用奥利普idase α进行酶替代疗法是 ASMD 患者的第一种也是唯一批准的疾病修饰疗法。肺移植和造血干细胞移植也在 ASMD 的文献中有描述。NPD 型 C 中唯一批准的疾病修饰疗法是米格列司他，一种底物还原治疗。本综述的目的是阐述 NPD 的遗传基础和肺部受累的最新进展，重点介绍疾病的临床表现、影像学和组织病理学特征以及可用的治疗选择，并关注未来的治疗策略。
