The purpose of this study is to determine whether thymus transplantation without immunosuppression is effective in treating typical DiGeorge syndrome.

There is no safe and effective treatment for DiGeorge syndrome and most patients die by the age of two. For patients with a severe T cell defect, the PI has shown that thymus transplantation is safe and efficacious under other clinical protocols. Complete DiGeorge syndrome is characterized by very low T cell or very low naïve T cell numbers. In this study, typical complete DiGeorge syndrome subjects receive human postnatal cultured thymus tissue transplants. Thymus tissue that would otherwise be discarded is transplanted into DiGeorge subjects in the operating room. At the time of transplantation, a skin biopsy is obtained look for any preexisting T cells. After transplantation, subjects are followed by routine research immune evaluations, using blood samples obtained every 2-4 weeks. At approximately 2-3 months post-transplantation subjects undergo an open biopsy of the allograft. The biopsy is done under general anesthesia in the operating room. At the time of the graft biopsy, another skin biopsy is obtained to look for clonal populations of T cells.

The protocol aims include: assessing thymopoiesis in the allograft biopsy; assessing immunoreconstitution of complete DiGeorge syndrome subjects after postnatal allogeneic thymus transplantation; assessing minimally invasive methods of assessing thymopoiesis (flow cytometry and polymerase chain reaction (PCR)); assessing pre-transplant T cells which do not proliferate in response to mitogens (focusing on NK-T cells); and, assessing thymus transplantation safety and toxicity.

• Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007 May 15;109(10):4539-47. Epub 2007 Feb 6.
• Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Haynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003 Aug 1;102(3):1121-30. Epub 2003 Apr 17.

Inclusion Criteria:

• Diagnosis of complete DiGeorge syndrome which is either: T cells with < 50/mm3 with naive phenotype; or > 5% CD3 + T cells with naive T cell phenotype.
• Diagnosis of typical DiGeorge syndrome phenotype: > 50 T cells/cumm and very low proliferative responses to mitogens (e.g. < 20 fold response to mitogen phytohemagglutinin).
• Proliferative response to PHA > 20 fold above background or < 5000 counts per minute(cpm), whichever is higher.

{Note: Subjects with PHA responses 20 fold or more over background or > 5,000 cpm, whichever is higher, may be enrolled in another thymus transplant protocol.}

• Must have heart disease; hypocalcemia requiring replacement; 22q11 or 10p13 hemizygosity; CHARGE association; or must be child of diabetic mother and have abnormal ears.

Exclusion Criteria:

• Those who do not meet inclusion criteria
• Atypical DiGeorge syndrome phenotype
• Rash indicating atypical DiGeorge syndrome phenotype.