Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakif Gureba Cad., 34093, Fatih/Istanbul, Turkey.
Division of Child Neurology, Department of Neurology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
Neurol Sci. 2018 Dec;39(12):2123-2128. doi: 10.1007/s10072-018-3556-2. Epub 2018 Sep 12.
Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal storage disorder involving the white matter of the peripheral and the central nervous systems. It is caused by a deficiency of galactocerebrosidase enzyme activity. The most common manifestation is the classical early onset KD that leads to patient's loss before the age of 2. Herein, we report the evaluation of a consanguineous family with three affected children manifesting severe neurological findings that ended with death before the age of 2, in an attempt to provide genetic diagnosis to the family. One of the children underwent detailed physical and neurological examinations, including brain magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) evaluations. GALC genetic testing on this child enabled identification of a novel homozygous variant (NM_000153.3: c.1394C>T; p.(Thr465Ile)), which confirmed diagnosis as KD. Familial segregation of this variant was performed by PCR amplification and Sanger sequencing that revealed the parents as heterozygous carriers. We believe this novel GALC variant will not only help in genetic counseling to this family but will also aid in identification of future KD cases.
克拉伯病（KD）或球样细胞脑白质营养不良是一种常染色体隐性溶酶体贮积病，累及外周和中枢神经系统的白质。它是由半乳糖脑苷脂酶活性缺乏引起的。最常见的表现是经典的早发性 KD，导致患者在 2 岁之前死亡。在此，我们报告了一个近亲家庭的评估，该家庭有 3 个受影响的孩子表现出严重的神经学表现，最终在 2 岁之前死亡，试图为该家庭提供遗传诊断。其中一个孩子接受了详细的身体和神经检查，包括大脑磁共振成像（MRI）和头皮脑电图（EEG）评估。对这个孩子进行 GALC 基因检测，发现了一个新的纯合变异（NM_000153.3：c.1394C>T；p.（Thr465Ile）），这证实了 KD 的诊断。通过 PCR 扩增和 Sanger 测序对该变异进行了家族分离，结果显示父母为杂合子携带者。我们相信这个新的 GALC 变异不仅有助于对这个家庭进行遗传咨询，而且有助于识别未来的 KD 病例。
