Types A and B Niemann-Pick disease.
Types A and B Niemann-Pick disease.
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DOI：
10.1016/j.ymgme.2016.12.008
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发表时间：
2017-01
影响因子：
3.8
通讯作者：
Desnick RJ
中科院分区：
文献类型：
--
作者：
Schuchman EH;Desnick RJ
尼曼-匹克病（NPD）是指一组患者在组织中存在不同程度的脂质蓄积和泡沫细胞浸润，以及重叠的临床特征，包括肝脾肿大、肺功能不全和/或中枢神经系统（CNS）受累。由于罗斯科布雷迪和同事们的开创性工作，我们现在知道有两种不同的代谢异常导致NPD。第一种是由于酶酸性鞘磷脂酶（ASM;“A型和B型”NPD）的活性缺陷，第二种是由于胆固醇转运功能缺陷（“C型”NPD）。这里仅讨论A型和B型NPD。A型NPD患者在婴儿期表现出肝脾肿大和严重的CNS受累。它们很少能存活超过2-3岁。B型患者也有肝脾肿大和肺部病理改变，但通常没有中枢神经系统体征。B型患者的发病年龄和疾病进展速度差异很大，他们经常活到成年。中期患者也报告有轻度至中度神经系统检查结果。所有患有A型和B型NPD的患者在编码ASM（SMPD 1）的基因中具有突变，因此该疾病更准确地被称为ASM缺乏症（ASMD）。在此，我们将回顾A型和B型NPD的临床、病理、生化和遗传学发现，并强调布雷迪博士对这种疾病的开创性贡献。我们还将讨论这种疾病的治疗现状。
The eponym Niemann-Pick disease (NPD) refers to a group of patients who present with varying degrees of lipid storage and foam cell infiltration in tissues, as well as overlapping clinical features including hepatosplenomegaly, pulmonary insufficiency and/or central nervous system (CNS) involvement. Due to the pioneering work of Roscoe Brady and co-workers, we now know that there are two distinct metabolic abnormalities that account for NPD. The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM; “types A & B” NPD), and the second is due to defective function in cholesterol transport (“type C” NPD). Herein only types A and B NPD will be discussed. Type A NPD patients exhibit hepatosplenomegaly in infancy and profound CNS involvement. They rarely survive beyond 2–3 years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no CNS signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Intermediate patients also have been reported with mild to moderate neurological findings. All patients with types A and B NPD have mutations in the gene encoding ASM (SMPD1), and thus the disease is more accurately referred to as ASM deficiency (ASMD). Herein we will review the clinical, pathological, biochemical, and genetic findings in types A and B NPD, and emphasize the seminal contributions of Dr. Brady to this disease. We will also discuss the current status of therapy for this disorder.