title: Biochemical and Genetic Analysis of Seven Korean Individuals With Suspected Metachromatic Leukodystrophy.
abstract: Metachromatic leukodystrophy (MLD) is an autosomal recessive disease caused by a deficiency in arylsulfatase A (ARSA). However, decreased ARSA activity is also observed in pseudodeficiency (PD). To distinguish between MLD and PD, we performed gene mutation and sulfatide analyses by using dried blood spots (DBSs) from seven Korean individuals who underwent an analysis of ARSA activity. DNA was extracted from DBSs, and PCR-direct sequencing of ARSA was performed. The cDNA obtained was analyzed to confirm a novel mutation. Of the seven subjects, three were confirmed as having MLD, one was confirmed as having MLD-PD, one was confirmed as having PD, and the remaining two were obligate heterozygotes. We verified the novel pathogenic variant c.1107+1delG by performing familial and cDNA analyses. Sulfatide concentrations in DBSs were analyzed and were quantified by using ultra-performance liquid chromatography and tandem mass spectrometry, respectively. Total sulfatide concentration was inversely correlated with ARSA activity (Spearman's coefficient of rank correlation, P=0.929, P=0.0025). The results of this mutational and biochemical study on MLD will increase our understanding of the genetic characteristics of MLD in Koreans.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Minje
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Jun
authors.affiliation: Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea.
authors.forename: Yun-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
authors.forename: Baik-Lin
authors.initials: BL
authors.lastname: Eun
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hyung-Doo
authors.initials: HD
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. ; Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
mesh_terms: D000328:Adult; D002553:Cerebroside-Sulfatase / Q000172:deficiency / Q000235:genetics; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004252:DNA Mutational Analysis; D059788:Dried Blood Spot Testing; D005091:Exons; D056426:Genetic Loci; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012326:RNA Splicing; D013433:Sulfoglycosphingolipids / Q000032:analysis
chemical_list: D013433:Sulfoglycosphingolipids; D004247:DNA; D002553:Cerebroside-Sulfatase
keywords: Arylsulfatase A; Genetic mutation; Metachromatic leukodystrophy; Pseudodeficiency