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combined immunodeficiency (CID) - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

combined immunodeficiency

MONDO:0015131

Also known as:CIDcongenital combined immunodeficiencyX-linked combined immunodeficiency

Find Clinical TrialsTrials

Overview

A broad classification of inherited disorders presenting at birth that affect both the cell-mediated and humoral aspects of the immune response. Circulating numbers of B lymphocytes, T lymphocytes and NK cells are variable but where present do not function properly. Susceptibility to infection is the primary concern.

OnsetCHILDHOOD, INFANTILE, ADULT

Clinical Trials18 registered · 8 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: childhood, infancy, adulthood.

GeneReviews

Clinical Guidance

Individuals with ZAP70-related CID characteristically present in the first two years of life with recurrent bacterial, viral (including live-virus vaccine strains), and opportunistic infections, diarrhea, and failure to thrive. Severe lower-respiratory infections are seen, most notably Pneumocystis jiroveci infections and viral infections. Oral candidiasis is also common . Other presentations have also been reported:

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Suggestive Findings

ZAP70-related combined immunodeficiency (ZAP70-related CID) should be suspected in individuals who present with the following findings within the first two years of life:

Recurrent viral, bacterial, and opportunistic infections
Chronic diarrhea and failure to thrive
Characteristic results of lymphocyte subset analysis of CD3, CD4, and CD8 T cells, lymphocyte functional testing, and ZAP-70 protein expression (See Lymphocyte development and numbers.)

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for combined immunodeficiency. The disease remains an area of unmet medical need.

GeneReviews

Management Guidelines

Evaluations Following Initial Diagnosis

The care of individuals diagnosed with ZAP70-related CID is best managed with a multidisciplinary team of providers including hematology/oncology/bone marrow transplantation, immunology, genetics, and infectious disease specialists. To establish the extent of disease and needs in an individual diagnosed with ZAP70-related combined immunodeficiency (CID), the following evaluations are recommended:

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

Following a successful HSCT, the following should be routinely monitored:

Growth
Psychomotor development
Complete blood counts
Liver and renal function

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

18 clinical trials registered, 8 recruiting. Interventions under study include drug therapy, other interventions, biologic therapy, and gene therapy. Pipeline includes 1 PHASE2, 8 PHASE1, 2 NA. Research is primarily sponsored by academic and government institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT05651113](https://clinicaltrials.gov/study/NCT05651113)

Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 6:42 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:101972

GARD

Genetic and Rare Diseases Info Center

GARD:19806

Questions for Your Care Team

→Are any of the 18 active clinical trials a good fit for my situation?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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GeneReviews

Differential Diagnosis

Human immunodeficiency virus infection. Infants positive for human immunodeficiency virus (HIV+) may present with recurring infections and failure to thrive similar to CID. Individuals with HIV have CD4+ lymphopenia, in contrast to the CD8+ lymphopenia in individuals with ZAP70-related CID. In a neonate, the definitive diagnosis of HIV should be made by detection of cell-associated human immunodeficiency proviral DNA by polymerase chain reaction (PCR) amplification. See for additional considerations. Table 2. Combined Immunodeficiencies in the Differential Diagnosis of ZAP70-Related CID

Disorder	Gene Involved	Mode ofInheritance	Lymphocyte Phenotype
T	B	NK	Other ZAP70-related CID
ZAP70	AR	+	+
CD8A	AR	+	+
IL2RA	AR	+	+
MHC II deficiency (BLS)	See Major histocompatibility complex class II deficiency.	AR	+

Source: GeneReviews — "ZAP70-Related Combined Immunodeficiency"

Research Type	Count	% of Total
Research summaries	54	29%
Patient case studies	36	19%
Laboratory research	34	18%
Testing and diagnosis research	24	13%
Disease patterns and progression	20	11%
New treatment approaches	9	5%
Clinical study results	7	4%
Other research	3	2%

Kisho

combined immunodeficiency

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Treatment of Manifestations

Prevention of Primary Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Homozygous loss-of-function mutation in SIT1 leads to combined immunodeficiency due to dysregulated T cell receptor signaling.

combined immunodeficiency

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Management Guidelines

Evaluations Following Initial Diagnosis

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Treatment of Manifestations

Prevention of Primary Manifestations

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Recent Publications

Latest News & Developments

Homozygous loss-of-function mutation in SIT1 leads to combined immunodeficiency due to dysregulated T cell receptor signaling.