An observational study in AMPD3, OMIM*102772, AMP Deaminase Deficiency, AK1, OMIM *103000, Adenylate Kinase Deficiency and AMPD1, OMIM *102770, Myopathy Due to Myoadenylate Deaminase Deficiency, sponsored by National Human Genome Research Institute (NHGRI). Recruiting at 1 site in United States. Open to participants aged 1 Month to 100 Years. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by National Human Genome Research Institute (NHGRI) · Observational
Background:
Pyrimidine and purine metabolism disorders (DPPMs) affect how the body metabolizes chemicals called pyrimidines and purines. DPPMs can cause dysfunctions throughout the body, especially in the brain, blood, kidneys, and immune system. People with DPPMs might have no symptoms, mild symptoms, or they may have severe, chronic symptoms, that can be fatal. DPPMs are not well understood, and researchers want to learn more about what causes them and how to treat them.
Objective:
To learn more about factors that affect DPPMs by comparing test results from affected, uaffected family members, and healthy people.
Eligibility:
Three types of participants are needed: people aged 1 month and older with DPPMs; their family members who do not have DPPMs; and healthy volunteers.
Design:
Participants with DPPMs will come to the clinic once a year; some may be asked to come more often. At each visit, all affected participants will have a physical exam and give samples of blood, urine, saliva, and stool. Depending on their symptoms, they may also have other procedures, such as:
Swabs of their skin and inside the mouth.
Tests of their heart, kidney, brain, and nerve function.
Questionnaires about what they eat.
Dental exams, and exams of their hearing and vision.
Tests of their learning ability.
Monitoring of their physical activity.
Imaging scans.
Photographs of their face and body.
These tests may be spread over up to 7 days. Affected participants may remain in the study indefinitely if they wish to.
Healthy volunteers and family members will have 1 study visit. They will have a physical exam and may be asked to give blood, urine, saliva, and stool samples.
Study Description:
This study will explore the natural history and mechanisms of novel or known but incompletely characterized disorders of pyrimidine and purine metabolism (DPPMs). Eligible participants will be ascertained by identifying biochemical abnormalities in the levels of purines, pyrimidines and related compounds in body fluids, abnormal activity of enzymes, and/or identifying pathogenic variants in genes linked to purines and pyrimidine metabolism. We will collect participants DNA for genetic and genomic analyses, body fluids for biochemical analysis, blood and tissue samples for enzyme analysis, gastrointestinal samples for microbiome analysis. Some participants may undergo skin biopsy. Study subjects will be offered medical, laboratory, and imaging studies at the NIH Clinical Research Center consistent with the standards of care. Collected data will be analyzed to improve understanding of the natural history, develop statistical prediction models, identify and validate novel biomarkers.
Objectives:
Primary Objective: To describe features of novel and poorly characterized DPPMs.
Secondary Objectives: To identify genomic, clinical, pharmacological, laboratory, and dietary factors associated with variable outcomes in subjects affected by DPPMs.
Endpoints:
Primary Endpoint: Identify genomic variants, laboratory parameters, image findings, microbiome variables, nutritional and medication history of DPPMs.
Secondary Endpoints: Identify disease parameters associated with variable clinical outcomes (e.g., frequency of hospitalizations, survival, quality of life, function).
113 studies on the registry are indexed under Charcot-Marie-Tooth Disease; 38 are open to participants now.
This study's planned enrollment of 999 is above the median of 120 across 47 observational studies indexed under Charcot-Marie-Tooth Disease.
Browse Charcot-Marie-Tooth Disease studies →National Human Genome Research Institute (NHGRI) is the lead sponsor of 203 studies on the registry; 33 are open to participants now.
Counted across the registry records on this site, refreshed daily.
There are three populations that will be included in this study: 1. Subjects with known, suspected or uncharacterized DPPMs; 2. Family members of study subjects; 3. Healthy Volunteers;
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
There are three populations that will be included in this study: subjects with known DPPM, family members of study subjects, and healthy controls.
In order to be eligible to participate in this study as a subject with a known DPPM an individual must meet all following criteria:
At least one month of age;
In order to be eligible to participate in this study as an unaffected family member of a subject with known DPPM, an individual must meet all the following criteria:
In order to be eligible to participate in this study as an unrelated healthy volunteer, an individual must meet all the following criteria:
EXCLUSION CRITERIA:
Individuals meeting the following exclusion criteria are not eligible for the study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
1\. At least one month of age;2. Relationship either by blood or marriage, to an individual enrolled or about to be enrolled in the study with known or suspected DPPM;3. Likelihood, in the expert opinion of the study team, that analysis of a sample from the individual would advance genetic or functional analysis of the affected relative s possiblecondition; and4. Ability of the subject, parent/s (in the case of children), or an LAR to understand and the willingness to sign a written informed consent document.5. If during the consenting/assenting procedure, clinical suspicion arises that a family member has symptoms of the diagnosed DPPMs, additional review and/or studies may be requested to clarify the clinical status before enrolling a family member as an unaffected participant.
1\. No personal or family history of DPPMs;2. At least one month old;3. No symptoms of DPPMs;4. Likelihood, in the expert opinion of the study team, that a sample from the individual would advance the functional analysis of the DPPM under study; 5. And ability of the subject, parent/s (in the case of children), or an LAR to understand and the willingness to sign a written informed consent document.
1\. Regardless of gender, at least one month of age;2. A medical history that, in the expert opinion of the study team, is consistent with the DPPM; 3. Have a primary metabolic or genetic physician, or primary care provider; and 4. Ability of the subject, parent/s (in the case of children), or a Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
TP describe features of poorly characterized and novel DPPMs.
DPPMs demonstrate significant inter- and intra-familial variability. We hypothesize that differences in clinical outcomes are the result of differences in the genomic, laboratory, and nutritional determinates. A proportion of subjects with biochemical evidence of DPPMs do not have molecular confirmation, suggesting locus heterogeneity and the opportunity to identify novel DPPMs.
Time frame: indefinite
To identify genomic, clinical, pharmacological, laboratory, and dietary factors associated with variable outcomes in subjects affected by DPPMs.
The vast majority of DPPMs lack effective and definitive treatments. Identification of response biomarkers and candidate surrogate endpoints associated with clinical meaningful outcomes will enable future clinical trials for novel genomic medicines.
Time frame: indefinite
Plan to share: Undecided
Started Dec 2023 (actual). Primary completion is estimated for Jan 2099, 900 months after the start.
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