Enlarging the Nosological Spectrum of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids (HDLS)
Enlarging the Nosological Spectrum of Hereditary Diffuse Leukoencephalopathy with Axonal Spheroids (HDLS)
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DOI：
10.1111/bpa.12120
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发表时间：
2014-09-01
期刊：
影响因子：
6.4
通讯作者：
Stenzel, Werner
中科院分区：
文献类型：
--
作者：
Hoffmann, Sarah;Murrell, Jill;Stenzel, Werner
遗传性弥漫性脑白质病伴轴索球蛋白样变性（HDLS）是一种常染色体显性遗传病，临床表现为认知功能下降、人格改变、运动障碍、帕金森综合征和癫痫发作。最近，集落刺激因子-1受体（CSF 1 R）基因突变已被证明与HDLS相关。我们报告的临床，神经病理学和分子遗传学的结果，患者从一个新的家庭与突变的CSF 1 R基因。与既往报告的患者相比，疾病发作更早，疾病进展更快。男性患者以人格改变、酗酒、重度抑郁等精神症状为首发症状。在索引中，女性患者的初始症状是认知能力下降。磁共振成像（MRI）显示大脑双侧融合性白色病变。立体定向活检显示髓鞘丢失和小胶质细胞活化以及实质巨噬细胞浸润。存在大量轴突的球状体和球体。超微结构分析显示含色素的巨噬细胞。电镜下不仅在中枢神经系统（CNS），而且在皮肤神经中也发现了轴突样突起。我们在CSF 1 R基因中发现了一个杂合突变（c.2330G>A，p.R777Q）。通过这份报告，我们的目的是扩大HDLS的疾病谱，提供新的临床描述以及新的周围神经系统的神经病理学发现。
Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is an autosomal dominant disease clinically characterized by cognitive decline, personality changes, motor impairment, parkinsonism and seizures. Recently, mutations in the colony-stimulating factor-1 receptor (CSF1R) gene have been shown to be associated with HDLS. We report clinical, neuropathological and molecular genetic findings of patients from a new family with a mutation in the CSF1R gene. Disease onset was earlier and disease progression was more rapid compared with previously reported patients. Psychiatric symptoms including personality changes, alcohol abuse and severe depression were the first symptoms in male patients. In the index, female patient, the initial symptom was cognitive decline. Magnetic resonance imaging (MRI) showed bilateral, confluent white matter lesions in the cerebrum. Stereotactic biopsy revealed loss of myelin and microglial activation as well as macrophage infiltration of the parenchyma. Numerous axonal swellings and spheroids were present. Ultrastructural analysis revealed pigment-containing macrophages. Axonal swellings were detected by electron microscopy not only in the central nervous system (CNS) but also in skin nerves. We identified a heterozygous mutation (c.2330G>A, p.R777Q) in the CSF1R gene. Through this report, we aim to enlarge the nosological spectrum of HDLS, providing new clinical descriptions as well as novel neuropathological findings from the peripheral nervous system.