Table I.

Outline of Inclusion and Exclusion Criteria for Patient Eligibility and Assignment to Strata

Stratum A, Typical SCID

Patients who meet the following inclusion criteria and who received HCT as initial treatment are eligible for enrollment into Stratum A (Classic SCID) of the study: ▪Absence or very low number of T cells (CD3 T cells < 300/microliter), AND no or very low T cell function (< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA)              Or ▪T cells of maternal origin present

Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis

Patients who were treated initially with HCT and who meet the following criteria are eligible for enrollment into Stratum B of the study: Leaky SCID ▪Reduced number of CD3 T cells ❖for age up to 2 years < 1000/microliter ❖for > 2 years up to 4 years < 800/microliter ❖for > 4 years < 600/microliter ▪Absence of maternal engraftment ▪< 30% of lower limit of normal T cell function (as measured by response to PHA) Omenn Syndrome ▪Generalized Skin Rash ▪Absence of maternal engraftment. ▪Detectable CD3 T cells, ≥ 300/microliter ▪Absent or low (up to 30% of normal) T cell proliferation to antigens to which the patient has been exposed

If the proliferation to antigen was not performed, but at least 4 of the following 10 supportive criteria, at least one of which must be among those marked with an asterisk (*) below are present, the patient is eligible: ▪Hepatomegaly ▪Splenomegaly ▪Lymphadenopathy ▪Elevated IgE ▪Elevated absolute eosinophil count ▪*Oligoclonal T cells measured by CDR3 length or flow cytometry ▪* >80% of CD3+ or CD4+ T cells are CD45RO+ ▪*Proliferation to PHA is reduced <30% of lower limit of normal ▪*Proliferative response in mixed leukocyte reaction is reduced <30% of lower limit of normal ▪*Mutation in SCID-causing gene

Reticular Dysgenesis (RD) ▪Absence or very low number of T cells (CD3 T cells <300/microliter) ▪No or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (PHA) ▪Severe neutropenias (absolute neutrophil count <200/microliter) ▪Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination and/or a deleterious AK2 mutation

Stratum C, SCID with Non-HCT Treatments

Patients who met the above criteria for Stratum A or B and were initially treated with PEG-ADA ERT or gene therapy with autologous modified cells are eligible for enrollment into Stratum C (SCID with non-HCT treatments) of the study. ▪ADA Deficient SCID treated with PEG-ADA ERT. ▪Any SCID treated with gene therapy.

Exclusion Criteria (see Table E1)