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

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 d...

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Bibliographic Details
Published in:Journal of inherited metabolic disease 2015-09, Vol.38 (5), p.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: Article
Language:English
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
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Summary: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.
ISSN:0141-8955
1573-2665
DOI:10.1007/s10545-015-9828-6