Tongxia Zhang1, Chuanzhu Yan1,2,3, Kunqian Ji1, Pengfei Lin1, Lingyi Chi2,4, Xiuhe Zhao1, Yuying Zhao1. 1. Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Shandong University, Jinan 250012, China. 2. Brain Science Research Institute, Qilu Hospital, Shandong University, Jinan 250012, China. 3. Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao 266035, China. 4. Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan 250012, China.
Abstract
BACKGROUND: Krabbe disease (KD) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of the galactocerebrosidase (GALC) enzyme. The adult-onset KD is infrequent, and often presenting with slowly progressive spastic paraplegia. Herein, we describe a two-generation concomitant Chinese pedigree of adult-onset KD in which the proband presented with acute hemiplegia at onset. METHODS: We collected the clinical and neuroimaging data of the pedigree. GALC enzyme activity detection and gene analysis were performed to confirm the diagnosis. Moreover, we reviewed all studies available on PubMed to understand the correlationship between phenotype and genotype of the identified mutations. RESULTS: The proband presented with sudden-onset weakness of left limbs with selective pyramidal tract involvement on diffusion-weighted imaging (DWI) of brain MRI. The GALC enzyme activity of him was low, and the GALC gene analysis revealed compound heterozygous pathogenic mutations of c.1901T>C and c.1901delT. More interestingly, the homozygous c.1901T>C mutations were found in the proband's asymptomatic father and two paternal uncles. Meanwhile, the literature review revealed the c.1901T>C mutation was only found in the late-onset form of KD. CONCLUSIONS: These observations, combined with previous reports, indicate that KD should be considered in the adult patients presenting selective pyramidal tract impairment even with sudden onset.
BACKGROUND: Krabbe disease (KD) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of the galactocerebrosidase (GALC) enzyme. The adult-onset KD is infrequent, and often presenting with slowly progressive spastic paraplegia. Herein, we describe a two-generation concomitant Chinese pedigree of adult-onset KD in which the proband presented with acute hemiplegia at onset. METHODS: We collected the clinical and neuroimaging data of the pedigree. GALC enzyme activity detection and gene analysis were performed to confirm the diagnosis. Moreover, we reviewed all studies available on PubMed to understand the correlationship between phenotype and genotype of the identified mutations. RESULTS: The proband presented with sudden-onset weakness of left limbs with selective pyramidal tract involvement on diffusion-weighted imaging (DWI) of brain MRI. The GALC enzyme activity of him was low, and the GALC gene analysis revealed compound heterozygous pathogenic mutations of c.1901T>C and c.1901delT. More interestingly, the homozygous c.1901T>C mutations were found in the proband's asymptomatic father and two paternal uncles. Meanwhile, the literature review revealed the c.1901T>C mutation was only found in the late-onset form of KD. CONCLUSIONS: These observations, combined with previous reports, indicate that KD should be considered in the adult patients presenting selective pyramidal tract impairment even with sudden onset.
Authors: H Furuya; Y Kukita; S Nagano; Y Sakai; Y Yamashita; H Fukuyama; Y Inatomi; Y Saito; R Koike; S Tsuji; Y Fukumaki; K Hayashi; T Kobayashi Journal: Hum Genet Date: 1997-09 Impact factor: 4.132
Authors: J I Satoh; H Tokumoto; K Kurohara; M Yukitake; M Matsui; Y Kuroda; T Yamamoto; H Furuya; N Shinnoh; T Kobayashi; Y Kukita; K Hayashi Journal: Neurology Date: 1997-11 Impact factor: 9.910