• Thymus transplantation efficacy: survival is recorded. Immune reconstitution efficacy: T cell phenotypic and functional parameters are evaluated. This will be evaluated in descriptive fashion. [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
• Parental parathyroid transplantation efficacy: number of subjects who are off calcium and calcitriol supplementation. The time that calcium supplementation needs to be resumed is recorded. [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: No ]
• Safety. Particular attention on oligoclonal T cell development; pulmonary complications; infections; and autoimmune diseases. Dose is correlated with number of subjects who get rashes lasting >1 week with development of wheezing or oxygen requirement. [ Time Frame: Ongoing - Post-Transplantation ] [ Designated as safety issue: Yes ]
• Correlations between dose and other immune parameters and factors which might affect outcome including HLA matching and thymus donor heart defect. Evaluate whether HLA-DR matching results in increased total CD4 T cell numbers. [ Time Frame: 1 year post-transplantation & ongoing ] [ Designated as safety issue: No ]

One purpose of this study is to determine whether the amount of thymus tissue transplanted into DiGeorge syndrome infants has any effect on the immune outcome. Another purpose of this study is to determine whether parental parathyroid gland transplantation (in addition to thymus transplantation) can help both the immune and the calcium problems in DiGeorge infants with hypocalcemia.

DiGeorge syndrome is a congenital disorder in which infants are born with defects of the thymus, heart and parathyroid gland. Complete DiGeorge Syndrome is usually fatal within the first two years of life. This trial will evaluate the role of thymus tissue dose in thymus transplantation in complete (typical) DiGeorge syndrome infants, and will continue safety assessments done in the phase I trial. Studies conducted under this protocol may lead to a Biologic License Application for this procedure for this patient population.

DiGeorge infants who have successful thymus transplants but remain with hypoparathyroidism must go to the clinic for frequent calcium levels and to the hospital for calcium infusions; these infants are at risk for seizures from low calcium. Approximately ½ of infants with profound hypoparathyroidism will develop nephrocalcinosis. This protocol has a parental parathyroid transplant arm for complete DiGeorge infants with athymia and profound hypoparathyroidism.

• Other: Thymus Transplantation
• Other: Parathyroid Transplantation

• Experimental: Thymus Transplantation With Parathyroid Transplantation
• Experimental: Thymus Transplantation Without Parathyroid Transplantation

Thymus Transplant Inclusion:

• Typical DiGeorge Syndrome diagnosis
• On 2 separate tests must have > 50 CD3+ T cells/cumm (or > 50 CD3+ T cells/cumm that are CD62L+ CD45RA+), or < 5% naïve phenotype T cells
• Must have < 20 fold response to PHA (or < 5,000 cpm) on 2 separate tests
• Must have 1 of following: 22q11 or 10p13 hemizygosity; hypocalcemia requiring replacement; congenital heart defect; CHARGE association or CHD7 mutation; or abnormal ears plus mother with diabetes (type I, type II, gestational)

Exclusion Criteria:

• Must not be anticipated to need heart surgery 4 weeks prior or 3 months post-transplantation
• Present or past lymphadenopathy
• Rash associated with T cell infiltration of the dermis and epidermis
• Rejection by the surgeon or anesthesiologist as surgical candidate
• Lack of sufficient muscle tissue to accept transplant
• Prior attempts at immune reconstitution (e.g, BMT or thymus transplantation)
• HIV infection

Additional Inclusion Criteria for Parathyroid Transplant Recipient:

• 2 tests showing: intact parathyroid hormone (PTH) < 5 pg/ml when ionized calcium < 1.1 mmol/L
• 2 involved parents

Exclusion for Parathyroid Transplant Recipient:

• Parents do not meet enrollment criteria.
• Parent(s) decline to be parathyroid donor(s).

Parental Parathyroid Donor Inclusion:

• > 18 years old
• Answers all questionnaire items and meets safety screening criteria
• Normal serum calcium
• Normal PTH function
• HLA typing consistent with parentage
• Parent chosen for donation will share HLA-DR allele in thymus donor; if not applicable, then either parent will be selected (if meet all other criteria).
• Must not be on anticoagulation or can come off for donation/transplantation

Parental Parathyroid Donor Exclusion:

• Donor is only living involved parent or caretaker of the recipient
• Hypoparathyroidism - low parathyroid hormone (PTH) in presence of low serum calcium and high serum phosphate
• Hyperparathyroidism (or history of) - elevated PTH in presence of high serum calcium and low serum phosphate
• History of cancer
• Evidence of any of following: HIV-1, HIV-2, HTLV-1, HTLV-2, syphilis, hepatitis B, hepatitis C, West Nile virus, or Trypanosoma Cruzi (Chagas disease)
• Elevated AST, ALT, alkaline phosphatase > 3 times upper limit of normal
• History including receipt of a xenograft or risk factors for SARS, Mad Cow - Disease or smallpox. Note: if parent has Mad Cow Disease risk factors (but not active disease), parent(s) may give permission for transplantation.
• CMV positive urine
• Positive CMV IgM antibodies
• Positive IgM anti-EBV VCA
• On blood thinners and cannot stop for the parathyroid donation
• Elevated PT or PTT (> ULN)
• Platelets < 100,000
• Positive Toxoplasma IgM
• The donor will receive a history and physical; may be excluded based on PI's medical judgment
• Hemoglobin < 9 g/dl
• Infectious lesion on head or neck
• Goiter on ultrasound
• Abnormal fiberoptic laryngoscopy of vocal cords
• Pregnancy
• Positive HSV IgG is not an exclusion; however, post transplantation prophylaxis is needed
• Positive VZV IgG is not an exclusion; however, post transplantation prophylaxis is needed
• Medical concern of otolaryngologist
• Concern by medical psychologist or social worker including. Parents are interviewed together and separately regarding following areas: medical history; health habits; substance use; relationships and support; education/work history; mental status/psychological history; readiness for donation.
• Questionnaire (safety screening) responses can lead to exclusion.

Biological Mother of DiGeorge Subject Inclusion Criteria:

• Competent to provide consent
• Willing to provide blood for testing (No other inclusion/exclusion for mother)

• National Institutes of Health (NIH)
• Food and Drug Administration (FDA)