Gene mutations and clinical manifestations in children with glycogen storage disease type Ib
LIANG Cui-Li, LIU Li, SHENG Hui-Ying, JIANG Min-Yan, YIN Xi, MEI Hui-Fen, CHENG Jing, ZHANG Wen, FAN Li-Ping
Department of Endocrinology and Metabolism, Guangzhou Women and Children’s Medical Center, Guangzhou Medical College, Guangzhou 510623, China. liliuxia@hotmail.com
Abstract OBJECTIV: Glycogen storage disease type Ib (GSDIb) is caused by a deficiency of glucose-6-phosphate translocase (G6PT) activity due to SLC37A4 gene mutations. Most GSDIb patients have recurrent infections and inflammatory bowel disease, with poor prognosis. Detection of SLC37A4 gene mutations is of great significance for the diagnosis, subtyping and outcome prediction of GSD patients. This study aims to analyze SLC37A4 gene mutations in Chinese GSDIb patients and to investigate the relationship between its genotypes and clinical manifestations. METHODS: All exons and their flanking introns of SLC37A4 gene in 28 Chinese children with a primary diagnosis of GSDIb were screened by PCR combined with direct DNA sequencing to detect SLC37A4 gene mutations. RESULTS: Five SLC37A4 gene mutations were detected in 7 (25%) of the 28 children, i.e., p.Gly149Glu (9/13, 69%), p.Gly115Arg (1/13, 8%), p.Pro191Leu (1/13, 8%), c.959-960 insT (1/13, 8%) and c.870+5G>A (1/13, 8%). CONCLUSIONS: In this study, c.959-960 insT is a novel mutation and p.Gly149Glu is the most common mutation. p.Gly149Glu may be associated with severe infections in children with GSDIb.
LIANG Cui-Li,LIU Li,SHENG Hui-Ying et al. Gene mutations and clinical manifestations in children with glycogen storage disease type Ib[J]. CJCP, 2013, 15(8): 661-665.
LIANG Cui-Li,LIU Li,SHENG Hui-Ying et al. Gene mutations and clinical manifestations in children with glycogen storage disease type Ib[J]. CJCP, 2013, 15(8): 661-665.
Soty M, Chilloux J, Casteras S, Grichine A, Mithieux G, Gautier-Stein A. New insights into the organisation and intracellular localisation of the two subunits of glucose-6-phosphatase[J]. Biochimie, 2012, 94(3): 695-703.
[2]
Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, et al. Glucose-6-phosphatase deficiency[J]. Orphanet J Rare Dis, 2011, 6: 27.
Davit-Spraul A, Piraud M, Dobbelaere D, Valayannopoulos V, Labrune P, Habes D, et al. Liver glycogen storage diseases due to phosphorylase system deficiencies: diagnosis thanks to non invasive blood enzymatic and molecular studies[J]. Mol Genet Metab, 2011, 104(1-2): 137-143.
Foster JD, Nordlie RC. The biochemistry and molecular biology of the glucose-6-phosphatase system[J]. Exp Biol Med (Maywood), 2002, 227(8): 601-608.
[11]
Pan CJ, Chen SY, Lee S, Chou JY. Structure-function study of the glucose-6-phosphate transporter, an eukaryotic antiporter deficient in glycogen storage disease type Ib[J]. Mol Genet Metab, 2009, 96(1): 32-37.
[12]
Chen SY, Pan CJ, Lee S, Peng W, Chou JY. Functional analysis of mutations in the glucose-6-phosphate transporter that cause glycogen storage disease type Ib[J]. Mol Genet Metab, 2008, 95(4): 220-223.
[13]
Chen SY, Pan CJ, Nandigama K, Mansfield BC, Ambudkar SV, Chou JY. The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in glycogen storage disease type Ib and Ic[J]. FASEB J, 2008, 22(7): 2206-2213.
[14]
Cheung YY, Kim SY, Yiu WH, Pan CJ, Jun HS, Ruef RA, et al. Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase-beta[J]. J Clin Invest, 2007, 117(3): 784-793.
[15]
Kim SY, Jun HS, Mead PA, Mansfield BC, Chou JY. Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type Ib[J]. Blood, 2008, 111(12): 5704-5711.
[16]
Chou JY, Jun HS, Mansfield BC. Neutropenia in type Ib glycogen storage disease[J]. Curr Opin Hematol, 2010, 17(1): 36-42.
[17]
Annabi B, Hiraiwa H, Mansfield BC, Lei KJ, Ubagai T, Polymeropoulos MH, et al. The gene for glycogen-storage disease type 1b maps to chromosome 11q23[J]. Am J Hum Genet, 1998, 62(2): 400-405.
[18]
Garty BZ, Douglas SD, Danon YL. Immune deficiency in glycogen storage disease type 1B[J]. Isr J Med Sci, 1996, 32(12): 1276-1281.
[19]
Shieh JJ, Pan CJ, Mansfield BC, Chou JY. A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia[J]. J Biol Chem, 2003, 278(47): 47098-47103.
[20]
Soty M, Chilloux J, Casteras S, Grichine A, Mithieux G, Gautier-Stein A. New insights into the organisation and intracellular localisation of the two subunits of glucose-6-phosphatase[J]. Biochimie, 2012, 94(3): 695-703.
Lam CW, Chan KY, Tong SF, Chan BY, Chan YT, Chan YW. A novel missense mutation (P191L) in the glucose-6-phosphate translocase gene identified in a Chinese family with glycogen storage disease 1b[J]. Hum Mutat, 2000, 16(1): 94.
[23]
Das AM, Lucke T, Meyer U, Hartmann H, Illsinger S. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth[J]. Ann Nutr Metab, 2010, 56(3): 225-232.
