A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach
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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-RCAr 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.
KeywordsGalactose Transferrin Serum Transferrin Solute Carrier Family Muscular Hypotonia
Congenital disorder of glycosylation
Dulbecco’s phosphate-buffered saline
Early onset epileptic encephalopathy
High performance liquid chromatography
Matrix-assisted laser desorption/ionization
Magnetic resonance imaging
Nucleotide sugar transporters
Reverse transcription polymerase chain reaction
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- SLC family
Solute carrier family
We thank Maria Plate, Martina Herting and Ingrid Du Chesne for technical assistance. Vitaflo is acknowledged for providing D-galactose for oral supplementation.
Compliance with ethics guidelines
Conflict of interest
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000(5). Informed consent was obtained from all patients for being included in the study.
Additional informed consent was obtained from all patients for whom identifying information is included in this article.
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