title: A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach.
abstract: Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. Often, multisystem disorders with central nervous system involvement and a large variety of clinical symptoms occur. The main characteristics are developmental delay, seizures, and ataxia. In this paper we report the clinical and biochemical characteristics of a 5-year-old girl with a defective galactosylation of N-glycans, resulting in developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment. Next generation sequencing revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM 300896). While this mutation was found heterozygous, random X-inactivation of the normal allele will lead to loss of normal SLC35A2 activity in respective cells. The functional relevance of the mutation was demonstrated by complementation of UGT-deficient MDCK-RCA(r) and CHO-Lec8 cells by normal UGT-expression construct but not by the mutant version. The effect of dietary galactose supplementation on glycosylation was investigated, showing a nearly complete normalization of transferrin glycosylation.
authors.affiliation: Universitätsklinikum Münster, Klinik für Kinder-und Jugendmedizin, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dörre
authors.forename: M
authors.initials: M
authors.lastname: Olczak
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: P
authors.initials: P
authors.lastname: Sosicka
authors.forename: M
authors.initials: M
authors.lastname: Grüneberg
authors.forename: J
authors.initials: J
authors.lastname: Reunert
authors.forename: G
authors.initials: G
authors.lastname: Kurlemann
authors.forename: B
authors.initials: B
authors.lastname: Fiedler
authors.forename: S
authors.initials: S
authors.lastname: Biskup
authors.forename: K
authors.initials: K
authors.lastname: Hörtnagel
authors.forename: S
authors.initials: S
authors.lastname: Rust
authors.forename: T
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D000818:Animals; D016466:CHO Cells; D002675:Child, Preschool; D018981:Congenital Disorders of Glycosylation / Q000235:genetics* / Q000628:therapy*; D006224:Cricetinae; D003412:Cricetulus; D004252:DNA Mutational Analysis; D004285:Dogs; D005260:Female; D005690:Galactose / Q000627:therapeutic use; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D009004:Monosaccharide Transport Proteins / Q000172:deficiency / Q000235:genetics*; D010641:Phenotype; D000099237:UDP-Galactose Translocators
chemical_list: D005690:Galactose; D009004:Monosaccharide Transport Proteins; D000099237:UDP-Galactose Translocators