McGovern Margaret M, Avetisyan Ruzan, Sanson Bernd-Jan, Lidove Olivier
Department of Pediatrics, Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA.
Sanofi Genzyme, Cambridge, MA, USA.
Orphanet J Rare Dis. 2017 Feb 23;12(1):41. doi: 10.1186/s13023-017-0572-x.
Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration, leading to death typically by the age of 3 years, most often from respiratory failure. In contrast, the clinical phenotype and life expectancy of patients with NPD B may vary widely. Almost all patients have hepatosplenomegaly and an atherogenic lipid profile, and most patients have interstitial lung disease with progressive impairment of pulmonary function and hematologic abnormalities including cytopenias. Other common clinical manifestations include liver dysfunction, heart disease, skeletal abnormalities and growth delays. Some patients with ASMD who survive beyond early childhood have intermediate phenotypes (variant NPD B) characterized by combinations of non-neurologic and mild to severe neurologic symptoms. The physical and psychosocial burden of illness in patients with NPD B is substantial. Common symptoms include shortness of breath, joint or limb pain, abdominal pain, bleeding and bruising. The disease often leads to chronic fatigue, limited physical or social activity and difficulties in performing daily activities or work. Many patients die before or in early adulthood, often from pneumonia/respiratory failure or liver failure. Available treatments are limited to symptom management and supportive care. An enzyme replacement therapy currently in clinical development is expected to be the first treatment addressing the underlying pathology of the disease. Early diagnosis and appropriate management are essential for reducing the risk of complications. While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.
酸性鞘磷脂酶缺乏症（ASMD）是一种罕见的溶酶体贮积病，是由不同的SMPD1突变引起的常染色体隐性遗传病。历史上，ASMD被归类为尼曼-匹克病（NPD）的A型（NPD A）和B型（NPD B）。NPD A与一致的毁灭性病程相关，伴有快速进展的精神运动退化，通常在3岁前死亡，最常见的死因是呼吸衰竭。相比之下，NPD B患者的临床表型和预期寿命可能差异很大。几乎所有患者都有肝脾肿大和动脉粥样硬化性脂质谱，大多数患者有间质性肺病，伴有肺功能进行性损害和包括血细胞减少在内的血液学异常。其他常见临床表现包括肝功能障碍、心脏病、骨骼异常和生长发育迟缓。一些存活至幼儿期以后的ASMD患者具有中间表型（变异型NPD B），其特征为非神经症状和轻度至重度神经症状的组合。NPD B患者的身体和心理社会疾病负担很重。常见症状包括呼吸急促、关节或肢体疼痛、腹痛、出血和瘀伤。该疾病常导致慢性疲劳、身体或社交活动受限以及进行日常活动或工作困难。许多患者在成年前或成年早期死亡，通常死于肺炎/呼吸衰竭或肝衰竭。现有的治疗仅限于症状管理和支持性护理。目前正在临床开发的一种酶替代疗法有望成为第一种针对该疾病潜在病理的治疗方法。早期诊断和适当管理对于降低并发症风险至关重要。虽然关于ASMD的知识在不断发展，但仍需要更多关于ASMD及其在整个疾病谱中的自然史的证据，以提高疾病识别、及时诊断和适当的疾病管理水平。
