Inflammatory Bowel Disease and T cell Lymphopenia in G6PC3 Deficiency

被引:43
作者
Begin, Philippe [1 ,2 ,3 ,6 ,7 ]
Patey, Natalie [2 ,8 ]
Mueller, Pascal [1 ,2 ,4 ]
Rasquin, Andree [2 ,4 ]
Sirard, Alain [1 ,2 ,5 ]
Klein, Christoph [9 ]
Haddad, Elie [1 ,2 ,3 ,10 ]
Drouin, Eric [1 ,2 ,4 ]
Le Deist, Francoise [1 ,2 ,10 ]
机构
[1] CHU St Justine, Dept Pediat, Montreal, PQ H3T 1C5, Canada
[2] Univ Montreal, Montreal, PQ, Canada
[3] CHU St Justine, Dept Pediat, Div Immunol, Montreal, PQ H3T 1C5, Canada
[4] CHU St Justine, Dept Pediat, Div Gastroenterol, Montreal, PQ H3T 1C5, Canada
[5] CHU St Justine, Dept Pediat, Div Gen Pediat, Montreal, PQ H3T 1C5, Canada
[6] Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ, Canada
[7] Ctr Hosp Univ Montreal CHUM, Div Immunol, Montreal, PQ, Canada
[8] CHU St Justine, Dept Pathol, Montreal, PQ H3T 1C5, Canada
[9] Univ Munich, Univ Childrens Hosp, Munich, Germany
[10] CHU St Justine, Dept Immunol & Microbiol, Montreal, PQ H3T 1C5, Canada
关键词
G6PC3; congenital neutropenia; inflammatory bowel disease; lymphopenia; G6PT; thymic naive;
D O I
10.1007/s10875-012-9833-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose G6PC3 deficiency presents as a complex and heterogeneous syndrome that classically associates severe congenital neutropenia with cardiac and urogenital developmental defects. Here we investigate the findings of T cell lymphopenia and inflammatory bowel disease in a child with G6PC3 deficiency due to compound heterozygous mutations in intron 3 (c.IVS3-1 G>A) and exon 6 (c.G778G/C; p.Gly260/Arg). Methods Histological examination was conducted on all biopsy specimens. Immunophenotyping and lymphocyte proliferation assays were performed. Immunoglobulin levels and vaccine responses were measured. Results The patient showed persistent global T cell lymphopenia, with only 8 to 13 % of thymic naive CD31(+)CD45RA(+) cells among CD4 T cells (normal range 27-60 %). Proliferation assays and vaccine responses were within normal limits. The gastrointestinal inflammatory lesions were very closely related to those of glycogen storage disease type 1b, with a Crohn's-like appearance but without granuloma or increased cryptic abscesses. The gastrointestinal disease responded to infliximab therapy. These findings were associated with a polyclonal hypergammaglobuliemia G. Conclusion G6PC3 deficiency may present with inflammatory bowel disease and T cell lymphopenia. The diagnosis should thus be considered in a patient with chronic congenital neutropenia and gastrointestinal symptoms. Patients with confirmed disease should also undergo T cell phenotyping to rule out cellular immunodeficiency.
引用
收藏
页码:520 / 525
页数:6
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