Detection and Characterization of Neurologic Manifestations of Inborn and Acquired Errors of Immunity

* INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Aged \>=2 years. To be seen at the NIH CC, participants must be \>=3 years of age.
2. Willing to allow specimens and data to be stored for future research.
3. Willing to allow genetic testing on their biospecimens.
4. Able to provide informed consent (for ages \>=18 years) or has parent(s) or guardian(s) who can provide permission to participate on their behalf (for ages \<18 years).

   * Decisionally impaired affected adult participants may have a legally authorized representative (LAR) to provide informed consent on their behalf.

Additional Inclusion Criterion for Affected Participants:

Has a primary or acquired immunodeficiency and known or suspected infection or inflammation of the nervous system or post-infection sequelae, based on clinical or imaging data provided by the referral facility, or is at risk of developing such a neurologic complication. For the purpose of this study, neuroinfectious disease or neuroinflammation is defined as any of the following:

1. Any neurologic symptoms accompanied by CSF with evidence of inflammation (which may include pleocytosis, hypoglycorrachia, elevated protein, or other evidence of intrathecal immune activation, including immunoglobulin \[Ig\] G index or presence of oligoclonal bands).
2. Systemic infection or inflammatory disease with neurologic involvement.
3. Neuroimaging suggestive of infection or inflammation (for example, presence of contrast-enhancing lesions on CT or MRI).
4. Clinical presentation suggestive of infection or inflammatory process of the nervous system without better explanation.
5. History of infection or inflammatory process of the nervous system.

Affected participants must also have their own primary health care provider to manage their condition outside the NIH.

Additional Inclusion Criteria for Biological Relatives and Healthy Volunteers:

1. Is either a biological relative of an affected participant or is unrelated.
2. Does not have a known diagnosis of neuroinfectious disease or neuroinflammation.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Pregnant (for biological relatives and healthy volunteers).
2. Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.