Characteristics of patients with TTC7A deficiency undergoing HSCT
| Genotype . | Immunology . | Gut phenotype . | IS pre-HSCT . | Donor . | Stem cell source . | Conditioning regimen . | GVHD . | Chimerism . |
|---|---|---|---|---|---|---|---|---|
| Patient 1 | ||||||||
| p.Glu191fs | Low IgG levels | Pyloric stenosis | Steroids | Unrelated | CB | TBI 2 Gy | None | CD3 = 51% donor |
| p.I854Phe | Impaired mitogen stimulation | Microcolon | Azathioprine | HLA 8/10 | Cyclophosphamide 50 mg/kg | CD15 = 15% donor | ||
| Autoimmune enterocolitis (PE) | Infliximab | Fludarabine 200 mg/m2 | ||||||
| Daclizumab | ATG 7.5 mg/kg | |||||||
| Patient 2 | ||||||||
| p.Gly45_Ala55del | Low IgG levels | D/AC/TC atresias | Steroids | Sibling | BM | Treosulfan 42 g/m2 | Acute skin | CD3 = 100% donor |
| p.Gly45_Ala55del | Reduced TRECs | Microcolon | Infliximab | HLA 10/10 | Cyclophosphamide 120 mg/kg | Grade 1 | CD15 = 100% donor | |
| Autoimmune enterocolitis (PE) | Basiliximab | |||||||
| Cyclosporine | ||||||||
| Patient 3 | ||||||||
| p.Glu71Lys | Low IgG levels | Exomphalos | Steroids | Unrelated | PBSCs | Treosulfan 36 g/m2 | None | CD3 = 96% donor |
| p.Glu96 | Low T/NK cells | Pyloric/ileal atresias | HLA 12/12 | Fludarabine 150 mg/m2 | CD15 = 7% donor | |||
| Reduced TRECs | Microcolon | Alemtuzumab 1 mg/kg | ||||||
| Abnormal mitogen stimulation | Autoimmune enterocolitis (PE) | |||||||
| Patient 4 | ||||||||
| p.K606R | Low IgG levels | Pyloric stenosis | None | Sibling | BM | Equine ATG 30 mg/kg | None | CD3 = 100% donor |
| p.S672P | Low T cells | Jejunal and colonic atresias | HLA 9/10 | CD15 = 6% donor | ||||
| Absent TRECs | Microcolon | |||||||
| Abnormal mitogen stimulation |
| Genotype . | Immunology . | Gut phenotype . | IS pre-HSCT . | Donor . | Stem cell source . | Conditioning regimen . | GVHD . | Chimerism . |
|---|---|---|---|---|---|---|---|---|
| Patient 1 | ||||||||
| p.Glu191fs | Low IgG levels | Pyloric stenosis | Steroids | Unrelated | CB | TBI 2 Gy | None | CD3 = 51% donor |
| p.I854Phe | Impaired mitogen stimulation | Microcolon | Azathioprine | HLA 8/10 | Cyclophosphamide 50 mg/kg | CD15 = 15% donor | ||
| Autoimmune enterocolitis (PE) | Infliximab | Fludarabine 200 mg/m2 | ||||||
| Daclizumab | ATG 7.5 mg/kg | |||||||
| Patient 2 | ||||||||
| p.Gly45_Ala55del | Low IgG levels | D/AC/TC atresias | Steroids | Sibling | BM | Treosulfan 42 g/m2 | Acute skin | CD3 = 100% donor |
| p.Gly45_Ala55del | Reduced TRECs | Microcolon | Infliximab | HLA 10/10 | Cyclophosphamide 120 mg/kg | Grade 1 | CD15 = 100% donor | |
| Autoimmune enterocolitis (PE) | Basiliximab | |||||||
| Cyclosporine | ||||||||
| Patient 3 | ||||||||
| p.Glu71Lys | Low IgG levels | Exomphalos | Steroids | Unrelated | PBSCs | Treosulfan 36 g/m2 | None | CD3 = 96% donor |
| p.Glu96 | Low T/NK cells | Pyloric/ileal atresias | HLA 12/12 | Fludarabine 150 mg/m2 | CD15 = 7% donor | |||
| Reduced TRECs | Microcolon | Alemtuzumab 1 mg/kg | ||||||
| Abnormal mitogen stimulation | Autoimmune enterocolitis (PE) | |||||||
| Patient 4 | ||||||||
| p.K606R | Low IgG levels | Pyloric stenosis | None | Sibling | BM | Equine ATG 30 mg/kg | None | CD3 = 100% donor |
| p.S672P | Low T cells | Jejunal and colonic atresias | HLA 9/10 | CD15 = 6% donor | ||||
| Absent TRECs | Microcolon | |||||||
| Abnormal mitogen stimulation |
Additional data on histological evolution post-HSCT are in the supplemental Material.
ATG, antithymocyte globulin; BM, bone marrow; CB, cord blood; D/AC/TC, duodenum/ascending colon/transverse colon; GVHD, graft-versus-host disease; IgG, immunoglobulin G; IS, immune suppression; PBSC, peripheral blood stem cell; PE, panenteric (small and large bowel); TBI, total body irradiation.