Patients Treated for Chronic Granulomatous Disease (CGD) Since 1995

Inclusion Criteria:

• Participant Inclusion Criteria (Part 1 - Longitudinal Analysis)
• CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After 1988

1. CGD Patients will be Defined by both Defective Neutrophil NADPH OxidaseFunction and by Clinical History Consistent with CGD Patients must have both of: A functional assay demonstrating abnormal NADPH oxidase function (see Abelow); AND Clinical history consistent with CGD (see B below).

Patients must have both "A" and "B": A. Function: Assays of NADPH Oxidase Function I. Dihydrorhodamine (DHR) Assay:

• Blood sample was obtained at a time when patient was clinically stableand not critically ill, with control samples performed simultaneouslyindicating a qualified assay; and
• Assay unequivocally demonstrates CGD with an stimulation index (SI) SI < 35 or equivalent. Assay report, including mean fluorescence intensity (MFI) from unstimulated and stimulated samples and gating strategy,must be de-identified and provided. OR II. Nitroblue Tetrazolium Oxidation Test (NBT): o Diagnostic of CGD (reported as reduced granulocyte oxidative response).Report must be de-identified and provided. AND B. Clinical History: One or More of the Following:
• Severe and/or recurrent infection (liver, perirectal or lung abscess;pneumonia; adenitis; or osteomyelitis) due to, for example,Staphylococcus aureus, Burkholderia sp, Serratia marcescens,non-albicans Candida sp, Aspergillus sp or other mold; or Nocardia spor other deep tissue infection characteristic of CGD
• Sterile granulomatous disease in respiratory, gastrointestinal orurogenital tracts; or Crohn's disease-like colitis
• A family history consistent with either X-linked or autosomal recessiveCGD In cases where either functional assay (A) or history (B) is equivocal, oneor more of the following may be used to confirm a diagnosis of CGD: C. Absent or significantly reduced in expression or abnormal size of any ofthe 5 phox components (gp91 phox, p47 phox, p22 phox, p67phox, and p40phox)of NADPH oxidase, by either:
• Western blot
• Northern blot OR D. Mutation in a gene encoding one of the 5 phoxcomponents (gp91 phox, p47 phox, p22 phox, p67 phox, and p40 phox) ofNADPH oxidase that is predictive of a decreased or absent oxidativeburst. (Nonsense, frameshift, or previously described missense mutationassociated with CGD). Molecular Diagnosis is Desirable In addition, molecular diagnosis (genesequencing and expression analysis) of CGD is desirable and should beperformed when possible.

2. Further Characterization of Oxidase Level, Longitudinal Study, ProspectiveCohort Patients who are to undergo transplantation during the study periodmust be further characterized as oxidase-null or oxidase positive by levelof oxidase production by either:

• DHR assay stimulation Index: where SI ≤ 2.5 will be classified asoxidase-null CGD. Those with SI > 2.5 will be classified as oxidasepositive CGD. A single validated test that is accepted by the PID-CGDReview Panel is adequate, but testing on two occasions for validationis desirable. OR
• Ferricytochrome C reduction assay of granulocytes with O2 < 2.3 nmoles /106 cells/h classified as oxidase-null CGD. A single validated testthat is accepted by the PID-CGD Review Panel is adequate, but testingon two occasions for validation is desirable. OR o Genetic sequencing reporting a mutation that is unequivocally associatedto absent oxidase production. (e.g. null mutations) will be classified asoxidase-null CGD (See discussion in Appendix I for how family history,genotype and CGD mutation information will be applied to assigning patientslacking any quantitative oxidase activity measurements to residualoxidase-null or residual oxidase-positive groups).

3. Longitudinal Study, Retrospective Cohort Patients who have already beentransplanted will be included regardless of whether further characterizationby oxidase level (or genotype/mutation data) is possible or not.

• Non-Transplanted CGD Patients with Birth Year In or After 1988 A non-transplant (conventional therapy) group of CGD subjects will be enrolled in the longitudinalstudy. The non-transplant subjects will be selected from the potentially eligible (retrospective) patient cohort with diagnosis of CGD treated with conventionalnon-transplant therapy. Participating sites will enter their entire retrospectivecohort of CGD patients having birth year in or after 1988 into the registrationcohort for this protocol. Baseline for both non-transplant subjects and HCTsubjects for the purpose of comparing survival will be the year of birth.However, for non-transplant subjects, many of the detailed analyses such asinfection and autoimmune complication rates will be assessed in the yearpreceding the date of last contact.
• Participant Inclusion Criteria (Part 2 - Cross-Sectional Analysis) To participate inthe Cross-Sectional Analysis, patients must have previously been enrolled into theLongitudinal Analysis of Protocol 6903. All transplanted subjects in theCross-Sectional Analysis are surviving and shall have at least 3 years of follow-uppost-transplant to be included. Non-transplanted CGD subjects will become eligible forconsideration for the Cross-Sectional Analysis if they were eligible and enrolled inthe retrospective cohort of the Longitudinal Analysis, and if/when they are > 3 yearspost-diagnosis of CGD. Provision of written informed consent will be required forinclusion in the Cross-Sectional Analysis.

Exclusion Criteria:

• Participant Exclusion Criteria (Longitudinal and Cross- Sectional Analyses)
• Presence of other primary immunodeficiency syndromes that do not meet theclinical and laboratory criteria for CGD.
• Rac2 Deficiency
• Myeloperoxidase Deficiency (MPO Deficiency)
• Glutathione deficiency
• Leukocyte adhesion deficiency syndrome
• Non-transplant subjects:
• The above exclusions pertain.
• In addition, non-transplant subjects will be excluded if the only assessment ofoxidase function available is the nitroblue tetrazolium (NBT) test (anon-quantitative test).