TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children

Inclusion Criteria:

1. Patient with any form of primary immune deficiency/dysregulatory disorderscharacterized by aberrant immune function, abnormal hematopoiesis, systemic or organspecific autoimmunity and/or non-malignant lymphoproliferation. This includes, butnot limited to: I. Disorders of phagocytes: Chronic granulomatous disease, Leukocyte adhesiondeficiency, defects of IL-10 pathway, MonoMac syndrome II. Defects of cellular and humoral immunity: Severe Combined ImmunodeficiencyDisorder (infants with classic SCID up to 2 years of age will be excluded due toother open protocol), X-linked hyper-IgM syndrome, DOCK8 deficiency, ZAP70deficiency, common variable immunodeficiency (CVID), Wiskott-Aldrich syndrome, NEMOdeficiency. III. Disorder of immune dysregulation: Immunodysregulation polyendocrinopathyenteropathy X-linked (IPEX) syndrome, CTLA4 deficiency, LRBA deficiency, STAT1 GOF,STAT3 GOF, X-linked lymphoproliferative disease etc. IV. Other PIDs and immune dysregulatory disorders who can be benefitted by HCT asdeemed appropriate by the PI and the treating immunologist.

2. Histiocytic disorders including hemophagocytic lymphohistiocytosis (familial HLH (types 1-5), secondary HLH (refractory to therapy or with recurrent episodes ofhyper inflammation) and multisystem refractory Langerhans cell histiocytosis.

3. Metabolic disorders that could improve or stabilize after stem cell transplantationsuch as mucopolysaccharidoses, neurodegenerative disorders, osteopetrosis, etc.

Inclusion Criteria:

1. Patient has a suitable genotypic identical match of 5/10. The donor and recipientmust be identical, as determined by high resolution typing, at least one allele ofeach of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1.

2. Patients must have adequate organ function measured by:

3. Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 40% or SF ≥ 26%

4. Pulmonary: asymptomatic or if symptomatic DLCO ≥ 40% of predicted (correctedfor hemoglobin) or pulse oximetry ≥ 92% on room air if the patient is unable toperform pulmonary function testing.

5. Renal: Creatinine clearance (CrCl) or glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m2.

6. Hepatic: Serum conjugated (direct) bilirubin < 2.0 x ULN for age; AST and ALT < 5.0 x ULN for age.

7. Karnofsky or Lansky (age-dependent) performance score ≥ 50

8. Signed written informed consent

Exclusion Criteria:

1. Participants who have an HLA-matched sibling who is able and willing to donate bonemarrow. Patients with a HLA-matched unrelated donors are not excluded.

2. Pregnant or breastfeeding females.

3. Patient has HIV or uncontrolled fungal, bacterial or viral infections.

4. Patient has received prior solid organ transplant.

5. Patient has active GVHD (> grade II) or chronic extensive GVHD due to a previousallograft at the time of inclusion.