Natural History Study of SCID Disorders

• Stratum A, 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(Classic SCID):

• Absence or very low number (<300 /µL) of CD3+T cells, AND
• No or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (HLA) 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 not detected;
• AND either one or both of the following with rule-out of MHC Class I and II non- expression by flow cytometry (or histology):
• <30% of lower limit of normal T cell function (as measured by response to PHA),OR
• Absent or <10% of lower limit of normal proliferative responses to candida and tetanus toxoid antigens (post vaccination or exposure), with expression of HLA by flow/serology.
• AND either one or both of the following:
• ≥80% of CD3+ or CD4+ T cells are CD45RO+ (at ≤2 years of age), OR
• Genetic abnormality for SCID.
• AND does not meet criteria for Omenn Syndrome.

Omenn Syndrome:

• Generalized skin rash;
• Maternal lymphocytes not detected;

--Note: If maternal engraftment was not assessed and ruled out, the patient is not eligible as Omenn Syndrome.

• ≥80% of CD3+ or CD4+ T cells are CD45RO+ ( ≤ 2 years of age)
• Absent or low (< 30% lower limit of normal) T cell proliferation to antigens

NOTE: If proliferation to antigen was not performed, but at least 4 of the following 8 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 < 30% of lower limit of normal or SI < 20
• *Mutation to SCID causing gene.

Reticular Dysgenesis:

• <300/µL number of T cells (CD3 < 300 / µL);
• None or <10% lower limit of normal PHA proliferation;
• Severe neutropenia (absolute neutrophil count < 200 /µL); AND
• One or more of the following:
• Sensori-neural deafness OR
• Deficiency of marrow granulopoiesis on bone marrow examination OR
• A pathogenic mutation in the adenylate kinase 2 (AK2) gene identified.

Stratum C, SCID with Non-HCT Treatments. Subjects who meet the following criteria and the intention is to treat with PEG-ADA or gene transfer with autologous modified cells are eligible for enrollment into Stratum C:

• ADA Deficient SCID with intention to treat with PEG-ADA;
• ADA Deficient SCID with intention to treat with gene transfer; or
• X-linked SCID with intention to treat with gene transfer. Note: For subjects with presumed ADA SCID, T cell studies MUST be obtained prior to enzyme replacement therapy with PEG-ADA ERT or blood transfusion.