Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Department of Neurology, Nakamura Memorial Hospital, Sapporo, Japan.
Pathol Int. 2022 Nov;72(11):558-565. doi: 10.1111/pin.13275. Epub 2022 Oct 6.
Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Klüver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain.
克拉伯病是一种溶酶体贮积症，由半乳糖脑苷脂酶（GALC）缺乏引起，导致中枢和周围神经系统脱髓鞘。几乎所有克拉伯病患者都是婴儿，这是首例描述成人发病病例的病理发现报告。本文报道了 2 例尸检病例：1 例为 73 岁女性，1 例为 2 岁男性。成年发病患者在三十多岁后期出现症状，并通过 GALC D528N 和 L634S 突变的鉴定以及 T2 加权磁共振成像诊断；她在锥体束沿途的白质、双侧中央前回，以及从三角区到侧脑室后角处，信号增强。显微镜下，中央前回和枕叶-丘脑辐射的白质 Klüver-Barrera 染色苍白，观察到少数球样细胞。本成年发病病例中鉴定出的 GALC 突变并未完全使 GALC 酶活性失活，导致大脑局灶性脱髓鞘。
