Assessment of the Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease

• INCLUSION CRITERIA:

Subjects may be enrolled if they are:

1. Already are enrolled on an existing CGD protocol at the Clinical Center (and will remain enrolled on their existing protocol);
2. Are included in one of the study cohorts listed below;
3. Male or female;
4. Able to comply with self-administration of a subcutaneous injection; and
5. Willing to have their blood samples stored for the duration of this study and for future research.

Study Groups/Cohorts:

X-linked CGD Nonsense/Frameshift/RNA Processing/Deletion Mutations Cohort: Subjects in this cohort must have X-linked CGD resulting from a documented nonsense, frameshift, RNA processing, or deletion gene mutation. Subjects with other gene defects or for whom the specific genetic defect has not been determined are not eligible for inclusion in this cohort.

X-linked CGD Missense Mutation with Low Baseline Superoxide Production (less than or equal to 2.5 nmol/10(6) cells/hr) Cohort: Subjects in this cohort must have X-linked CGD resulting from a documented missense gene and superoxide production by cytochrome c reduction assay at baseline of less than or equal to 2.5 nmol/10(6) cells/hr. Subjects with other gene defects or for whom the specific genetic defect has not been determined are not eligible for inclusion in this cohort.

X-linked CGD Missense Mutation with Higher Baseline Superoxide Production (greater than 2.5 nmol/10(6) cells/hr) Cohort: Subjects in this cohort must have X-linked CGD resulting from a documented missense gene and superoxide production by cytochrome c reduction assay at baseline of greater than 2.5 nmol/10(6) cells/hr. Subjects with other gene defects or for whom the specific genetic defect has not been determined are not eligible for inclusion in this cohort.

Autosomal Recessive p47phox CGD Cohort: Subjects in this cohort must have autosomal recessive CGD resulting from a documented p47phox gene mutation. Subjects with other gene defects or for whom the specific genetic defect has not been determined are not eligible for inclusion in this cohort.

Autosomal Recessive p67phox CGD Cohort: Subjects in this cohort must have autosomal recessive CGD resulting from a documented p67phox gene mutation. Subjects with other gene defects or for whom the specific genetic defect has not been determined are not eligible for inclusion in this cohort.

EXCLUSION CRITERIA:

Subjects are excluded from the study who:

1. Have undergone successful bone marrow transplantation;
2. Had a serious adverse reaction to IFN gamma in the past;
3. Are pregnant or breast feeding;
4. Weigh less than 11 kg;
5. Are currently on therapy with INF gamma;

6. Have any of the following medical conditions:

   • Coronary artery disease;
   • Hepatic disease and/or liver enzymes elevated above 3 times normal;
   • Seizure disorder, or
   • Severe myelosuppression (absolute neutrophil count less than1000 cells/mm(3)).

Participation of Minors: During the treatment phase of the study, up to 290 mL blood will be required during one 8-week period. As such, participation by individuals under 11 kg is not allowed and certain testing will be limited based on the subject's weight at the time of enrollment. Subjects will be assigned to 1 of 4 blood collection schedules based on their weight at time of enrollment. These categories will be as follows: adults (over 30kg), participants 20-30 kg, participants 15-20 kg, and participants 11-15 kg.

Participation of Women: Exposure to IFN gamma by the developing human fetus may be detrimental. For this reason, women of childbearing-age will have a pregnancy test prior to undergoing study procedures. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should immediately inform study staff and her primary care physician.

Pregnancy and Lactation: The effects of IFN gamma therapy on the developing fetus and newborn infant have not been studied. Therefore, it is not recommended that subjects who are pregnant or breast-feeding receive IFN gamma and they will be excluded from this study.