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. 2021 Jan 6;58(1):122-128.
doi: 10.1002/jmd2.12195. eCollection 2021 Mar.

SLC37A4-CDG: Second patient

Matthew P Wilson  1 , Dulce Quelhas  2 , Elisa Leão-Teles  3 , Luisa Sturiale  4 , Daisy Rymen  5 , Liesbeth Keldermans  1 , Valérie Race  1 , Erika Souche  1 , Esmeralda Rodrigues  3 , Teresa Campos  3 , Emile Van Schaftingen  6 , François Foulquier  7 , Domenico Garozzo  4 , Gert Matthijs  1 , Jaak Jaeken  5
Affiliations

SLC37A4-CDG: Second patient

Matthew P Wilson et al. JIMD Rep. .

Abstract

Recently, a disorder caused by the heterozygous de novo c.1267C>T (p.R423*) substitution in SLC37A4 has been described. This causes mislocalization of the glucose-6-phosphate transporter to the Golgi leading to a congenital disorder of glycosylation type II (SLC37A4-CDG). Only one patient has been reported showing liver disease that improved with age and mild dysmorphism. Here we report the second patient with a type II CDG caused by the same heterozygous de novo c.1267C>T (p.R423*) mutation thereby confirming the pathogenicity of this variant and expanding the clinical picture with type 1 diabetes, severe scoliosis, and membranoproliferative glomerulonephritis. Additional clinical and biochemical data provide further insight into the mechanism and prognosis of SLC37A4-CDG.

Keywords: CDG; G6PT1; SLC37A4; glycogen storage disease; glycosylation; hepatopathy.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Abnormal glycosylation of serum transferrin in a patient with SLC37A4‐CDG caused by the heterozygous c.1267C>T; p.R423* mutation. A, Photograph of the patient at 3 years of age. B, Capillary zone electrophoresis results, indicating a type 2 pattern. C, matrix‐assisted laser desorption ionization‐time of flight (MALDI‐TOF) mass spectrum (linear mode and negative polarity) of acidic N‐glycans from serum transferrin. Abnormal N‐glycans include: *SiaGalGlcNAcMan3GlcNAc2; **SiaGalGlcNAcMan4GlcNAc2; ***SiaGalGlcNAcMan5GlcNAc2. Symbols represent sugar residues as follows: blue square, N‐acetylglucosamine; green circle, mannose; yellow circle, galactose; purple diamond, sialic acid; red triangle, fucose
FIGURE 2
FIGURE 2
Matrix‐assisted laser desorption ionization‐time of flight‐mass spectrometry (MALDI‐TOF‐MS) spectra of the permethylated N‐glycans from HEK control cells following swainsonine treatment. Only the representative glycan structures are shown. Those resulting from swainsonine treatment are highlighted in a red square. Symbols represent sugar residues as follows: blue square, N‐acetylglucosamine; green circle, mannose; yellow circle, galactose; purple diamond, sialic acid; red triangle, fucose. Linkages between sugar residues have been removed for simplicity
See this image and copyright information in PMC

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