RESUMO
BACKGROUND: The most frequent and common form of Krabbe disease (KD) is early-onset KD in infants, and late-onset KD has been reported to be a rare disease. In the present study, we reported an adult-onset KD patient in a consanguineous Chinese family. METHODS: Clinical and radiological data were collected for a family pedigree. The patient was diagnosed with late-onset KD through next-generation sequencing. The result was confirmed by Sanger sequencing. GALC enzyme activity was also examined by the colorimetry method. Both the grey matter volume (GMV) and white matter volume values were examined and compared with the average values from ten age-matched normal controls. Moreover, we reviewed all the available KD studies on PubMed to understand the correlation between the phenotype and genotype of the identified mutation. RESULTS: The main manifestations of the proband were sudden onset seizures and cognitive decline. Mutation analysis of the GALC revealed a homozygous c.1901T>C mutation in exon 16, which resulted in an amino acid change in p.L634S. Sanger sequencing results showed that the homozygous mutation was inherited from the patient's parents, both of whom were revealed to be heterozygous carriers. Moreover, a decrease in GALC enzyme activity was also detected. However, no abnormal signals were found in the brain MRI. Further structural MRI analysis revealed a significantly decreased GMV in the proband compared to the normal controls. Moreover, it is of interest that all patients with the c.1901T>C mutation had late-onset KD and were selected from Asian countries, especially Japan and China. CONCLUSIONS: This patient with a homozygous GALC mutation expands the clinical presentation and characteristics of adult-onset KD, as indicated by grey matter atrophy without abnormal white matter signals.