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

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

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-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.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

CDG:

Congenital disorder of glycosylation

DPBS:

Dulbecco’s phosphate-buffered saline

EEG:

Electroencephalography

EOEE:

Early onset epileptic encephalopathy

ER:

Endoplasmic reticulum

ESI:

Electrospray ionization

HPLC:

High performance liquid chromatography

IEF:

Isoelectric focusing

IMPP:

Immunoprecipitation

MALDI:

Matrix-assisted laser desorption/ionization

MRI:

Magnetic resonance imaging

NSTs:

Nucleotide sugar transporters

OAE:

Otoacoustic emissions

RT-PCR:

Reverse transcription polymerase chain reaction

SDS-PAGE:

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

SLC family:

Solute carrier family

TF:

Transferrin

UGT:

UDP-galactose transporter

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Acknowledgments

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

ᅟ

Conflict of interest

None.

Informed consent

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.

Author information

Authors and Affiliations

  1. Universitätsklinikum Münster, Klinik für Kinder-und Jugendmedizin, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany

    K. Dörre, M. Grüneberg, J. Reunert, G. Kurlemann, B. Fiedler, S. Rust & T. Marquardt

  2. Laboratory of Biochemistry, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland

    M. Olczak & P. Sosicka

  3. Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan

    Y. Wada

  4. Praxis für Humangenetik und CeGaT GmbH, Tübingen, Germany

    S. Biskup & K. Hörtnagel

Authors
  1. K. Dörre
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  2. M. Olczak
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  3. Y. Wada
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  4. P. Sosicka
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  5. M. Grüneberg
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  6. J. Reunert
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  7. G. Kurlemann
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  8. B. Fiedler
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  9. S. Biskup
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  10. K. Hörtnagel
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  11. S. Rust
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  12. T. Marquardt
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Corresponding author

Correspondence to T. Marquardt.

Additional information

Communicated by: Eva Morava

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Dörre, K., Olczak, M., Wada, Y. et al. A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach. J Inherit Metab Dis 38, 931–940 (2015). https://doi.org/10.1007/s10545-015-9828-6

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  • DOI: https://doi.org/10.1007/s10545-015-9828-6

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