Bjurulf Björn, Spetalen Signe, Erichsen Aage, Vanier Marie T, Strøm Erik H, Strømme Petter
Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
Med Sci Monit. 2008 Aug;14(8):CS71-5.
Niemann-Pick disease type C1 (NPC1) and type C2 (NPC2) display the same pattern of neurovisceral storage due to deficiencies within lysosomes. NPC2 is a much rarer condition, and as reports on the pathological changes are scarce, the morphological findings in the lungs and brain in two siblings who died at an early age from pulmonary involvement are described. The diagnosis of NPC2 was confirmed at postmortem mutational analysis.
Both siblings presented with postnatal conjugated hyperbilirubinemia. They subsequently developed progressive respiratory insufficiency with opacification of the lungs on X-ray examination and died at the ages of 8 and 13 months. The lungs contained intra-alveolar accumulation of periodic acid-Schiff positive material, foamy macrophages, and hyperplasia of the alveolar cells, consistent with pulmonary alveolar lipoproteinosis. On neuropathological examination, storage material in swollen perikarya in the deep cerebellar nuclei, thalamus, medulla oblongata, and in the paravertebral ganglion cells was found. Meganeurites were present in the cerebral cortex. A few axonal spheroids were also observed. There seemed to be a reduced number of Purkinje cells in the cerebellum.
Evidence that NPC2 is associated with severe pulmonary alveolar lipoproteinosis is supported. There were extensive neuropathological changes with storage material in swollen perikarya and a few axonal spheroids.
由于溶酶体功能缺陷，尼曼-匹克病C1型（NPC1）和C2型（NPC2）表现出相同的神经内脏贮积模式。NPC2是一种更为罕见的疾病，由于关于其病理变化的报道较少，本文描述了两名因肺部受累早夭的同胞兄弟姐妹肺部和脑部的形态学发现。NPC2的诊断在尸检突变分析中得到证实。
两名同胞均表现为出生后结合胆红素血症。随后，他们逐渐出现进行性呼吸功能不全，X线检查显示肺部有混浊，分别于8个月和13个月时死亡。肺部存在肺泡内周期性酸-希夫染色阳性物质积聚、泡沫状巨噬细胞以及肺泡细胞增生，符合肺泡蛋白沉积症。神经病理学检查发现，在小脑深部核团、丘脑、延髓以及椎旁神经节细胞的肿胀核周体中有贮积物质。大脑皮质中存在巨神经突。还观察到一些轴突球。小脑浦肯野细胞数量似乎减少。
支持NPC2与严重肺泡蛋白沉积症相关的证据。存在广泛的神经病理学改变，肿胀核周体中有贮积物质以及一些轴突球。
