GM1 gangliosidosis is a storage disorder with autosomal recessive inheritance caused by deficiency of β‐galactosidase (GLB1), which is a lysosomal hydrolase, due to mutations in GLB1. We describe here an autopsy case of GM1 gangliosidosis in a female patient who survived for 38 years with a long period of artificial respiratory support (ARS). She was born after a normal pregnancy and delivery. Although development was normal until one year old, she was unable to walk at two years old and started having seizures by nine years old. At 21 years old, she became unable to communicate and was bed‐ridden. At 36 years old, she suffered from pneumonia and required ARS. She died of pneumonia at 40 years old. Neuropathological examination revealed severe atrophy, predominantly found in the frontal lobes. Microscopically, severe gliosis and neuronal loss were observed in the cerebral cortex, putamen, cerebellum, the latter including Purkinje cell and granule cell layers. The hippocampus was relatively preserved. Severe neuronal swelling was observed in the limbic regions and stored a material in these neurons negative for periodic acid‐Schiff (PAS). A PAS‐positive granular storage material in neurons and macrophages was mainly observed in the brainstem and limbic regions. Exome analysis showed a known c.152T>C (p.I51T) variant that has been described in type III patients and a novel c.1348‐2A>G variant in GLB1. Detailed analysis of reverse transcription‐polymerase chain reaction products of GLB1 mRNA revealed that these variants were present in a compound heterozygous state. In our case, clinical features and neuropathological findings were most consistent with type II, although the entire course was longer than any previously reported cases. This may be explained by the residual enzyme activity in this patient whose severity lay between types II and III. Our finding of relative preservation of the limbic regions suggests that neuronal loss in GM1 gangliosidosis has regional selectivity.

中文翻译：

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1例人工呼吸支持长期存活患者GM1型神经节苷脂贮积症II型尸检

GM1 神经节苷脂贮积症是一种常染色体隐性遗传的贮积症，由 GLB1 突变导致的 β-半乳糖苷酶 (GLB1)（一种溶酶体水解酶）缺乏引起。我们在此描述一例 GM1 神经节苷脂沉着症的尸检病例，该患者在长期人工呼吸支持 (ARS) 的情况下存活了 38 年。她是在正常怀孕和分娩后出生的。尽管一岁前发育正常，但她在两岁时无法行走，并在九岁时开始癫痫发作。21岁那年，她变得无法沟通并且卧床不起。36 岁时，她患有肺炎并需要 ARS。她40岁时死于肺炎。神经病理学检查显示严重萎缩，主要见于额叶。微观上，在大脑皮层、壳核、小脑中观察到严重的神经胶质增生和神经元丢失，后者包括浦肯野细胞和颗粒细胞层。海马体相对保存完好。在边缘区域观察到严重的神经元肿胀，并在这些神经元中储存了一种对高碘酸-希夫 (PAS) 呈阴性的物质。神经元和巨噬细胞中的 PAS 阳性颗粒储存物质主要在脑干和边缘区域观察到。外显子组分析显示已知的 c.152T>C (p.I51T) 变异已在 III 型患者中描述，并在 GLB1 中发现新的 c.1348-2A>G 变异。对 GLB1 mRNA 的逆转录聚合酶链反应产物的详细分析表明，这些变体以复合杂合状态存在。在我们的例子中，临床特征和神经病理学发现与 II 型最一致，尽管整个病程比以前报告的任何病例都要长。这可以通过该患者的残留酶活性来解释，其严重程度介于 II 型和 III 型之间。我们对边缘区域相对保留的发现表明 GM1 神经节苷脂病中的神经元丢失具有区域选择性。