A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach

• Published in: Journal of inherited metabolic disease Vol. 38; no. 5; pp. 931 - 940
• Main Authors: Dörre, K., Olczak, M., Wada, Y., Sosicka, P., Grüneberg, M., Reunert, J., Kurlemann, G., Fiedler, B., Biskup, S., Hörtnagel, K., Rust, S., Marquardt, T.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.09.2015; Blackwell Publishing Ltd
• Subjects: Animals; Biochemistry; Child, Preschool; CHO Cells; Congenital Disorders of Glycosylation - genetics; Congenital Disorders of Glycosylation - therapy; Cricetinae; Cricetulus; DNA Mutational Analysis; Dogs; Female; Galactose - therapeutic use; Human Genetics; Humans; Internal Medicine; Madin Darby Canine Kidney Cells; Medicine; Medicine & Public Health; Metabolic Diseases; Monosaccharide Transport Proteins - deficiency; Monosaccharide Transport Proteins - genetics; Original Article; Pediatrics; Phenotype; Transferrin; Serum Transferrin; Galactose; Muscular Hypotonia; Solute Carrier Family
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-015-9828-6

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.