The goal of this observational study is to learn about changes in health in children that develop over time that may impact overall health and a healthy lifespan. The main questions it aims to answer are:

• What are the changes in health that impact overall health and lifespan in children; and
• What test(s) are best at finding changes in health in children?

The two parts of the PUER Research study include (1) Baseline health assessment and (2) blood tests including genetic, molecular, and laboratory profiling. The Baseline assessment will consist of a health history questionnaire interview. Genetic assessment will be conducted using peripheral blood samples. Molecular and laboratory assessments will be conducted using peripheral blood samples and, potentially, urine, stool, and/or saliva samples.

The study will result in cross-sectional and longitudinal real world data collection to inform if any tests used can inform of health changes for individuals and may predict long-term health outcomes. Researchers at study sites will not be blinded to the data being collected during this study.

Inclusion Criteria:

To participate in the study, patients must meet the following criteria:

1. Male or non-pregnant female; age 6 to less than 18.

2. Females of childbearing potential (WOCBP) must have a negative urine pregnancy test (UPT) at all visits.

3. Presence of

   1. At least one pathogenic genetic variant in a biological parent, which is annotated as pathogenic in at least one public database, such as dbSNP, ClinVar, VEP (variant effect predictor), etc.; OR
   2. Presence of unexplained disease, illness, trait, or phenotype.

4. Approval is at the sole discretion of the sponsor.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from study participation:

1. Unwillingness or inability to participate in the study.
2. Unwillingness or inability to provide assent as per inclusion criterion #1, including those who lack the capacity to provide assent and will obtain 18 years of age prior to completion of the study.
3. WOCBP a with positive pregnancy test at enrollment or at any visit.

Male or non-pregnant female; age 6 to less than 18.