Clinical feature, GALC variant spectrum, and genotype–phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years

Abstract

AbstractKrabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype–phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months–34 years) and the most common phenotype was adult‐onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30‐kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later‐onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult‐onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.