Natural History Study of SCID Disorders

Inclusion Criteria: Stratum A: Typical SCID (formerly referred to as Classic SCID)- -Subjects who meet the following inclusion criteria and the intention is to treat with allogeneic hematopoietic cell transplant (HCT) are eligible for enrollment into Stratum A (Typical 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- -Subjects who meet the following criteria and the intention is to treat with HCT are eligible for enrollment into Stratum B: Leaky SCID: * Maternal lymphocytes tested for and not detected AND * Either one or both of the following (a,b) : * a.) \<50% of lower limit of normal T cell function as measured by response to PHA, OR response to anti-CD3/CD28 antibody * b.) Absent or \<30% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens * AND at least two of the following (a through e): * a.) Reduced number of CD3 T cells * age ≤2 years: \<1500/microliter * age \>2 years and ≤4 years: \<800/microliter * age \>4 years: \<600/microliter * b.) ≥80% of CD3+ or CD4+ T cells that are CD45RO+ * AND/OR \>80% of CD3+ or CD4+ T cells are CD62L negative * AND/OR \>50% of CD3+ or CD4+T cells express HLA-DR (at \<4 years of age) * AND/OR are oligoclonal T cells * c.) Hypomorphic mutation in IL2RG in a male, or homozygous hypomorphic mutation or compound heterozygosity with ≥1 hypomorphic mutation in an autosomal SCID-causing gene * d.) Low T Cell Receptor Excision Circles (TRECs) and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal. * e.) Functional testing in vitro supporting impaired, but not absent, activity of the mutant protein, AND * Does not meet criteria for Omenn Syndrome. Omenn Syndrome: * Generalized skin rash * Maternal lymphocytes tested for and not detected; --Note: If maternal engraftment was not assessed and ruled out, the subject is not eligible as Omenn Syndrome. * ≥80% of CD3+ or CD4+ T cells are CD45RO+ AND/OR * 80% of CD3+ or CD4+T cells are CD62L negative AND/OR * 50% of CD3+ or CD4+ T cells express HLA-DR (at \<2 years of age); * Absent or low (\< 30% lower limit of normal) T cell proliferation response to antigens (Candida, tetanus) to which the subject has been exposed NOTE: If proliferation to antigen was not performed, but at least 4 of the following 9 supportive criteria, at least one of which must be among those marked with an asterisk (\*) below are present, the subject is eligible as Omenn Syndrome: * Hepatomegaly * Splenomegaly * Lymphadenopathy * Elevated IgE * Elevated absolute eosinophil count * \*Oligoclonal T cells measured by CDR3 length or flow cytometry * \*Proliferation to PHA is reduced \<50% of lower limit of normal or SI \<30 * \*Hypomorphic mutation in a SCID causing gene * Low TRECS and/or the percentage of CD4+/45RA+/CD31+ or CD4+/45RA+/CD62L+ cells is below the lower limit of normal. Reticular Dysgenesis: * Absence or very low number of T cells (CD3 \<300/µL * No or very low (\<10% lower limit of normal) T cell response to PHA * Severe neutropenia (absolute neutrophil count \< 200 /µL) AND * ≥2 of the following (a,b,c): * a.) Sensori-neural deafness * b.) Deficiency of marrow granulopoiesis on bone marrow examination * c.) A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified. Stratum C: Subjects who meet the following criteria and the intention is to treat with therapy other than allogeneic HCT, primarily PEG-ADA ERT or gene therapy with autologous modified (gene transduced) cells, are eligible for enrollment into Stratum C: * ADA Deficient SCID with intention to treat with PEG-ADA ERT * ADA Deficient SCID with intention to treat with gene therapy * X-linked SCID with intention to treat with gene therapy * Any SCID patient previously treated with a thymus transplant (includes intention to treat with HCT, as well as PEG-ADA ERT or gene therapy) * Any SCID patient who received therapy for SCID deemed "non-standard" or "investigational", including in utero procedures. Exclusion Criteria: -Subjects who meet any of the following exclusion criteria are disqualified from enrollment in Strata A, B, or C of the study: * Presence of an Human Immunodeficiency Virus (HIV) infection (by PCR) or other cause of secondary immunodeficiency * Presence of DiGeorge syndrome * MHC Class I and MHC Class II antigen deficiency, and * Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency or transcobalamin deficiency.