Recruiting

Observational Study

Sponsor:

National Human Genome Research Institute (NHGRI)

Code:

NCT06092346

Conditions

AMPD3, OMIM*102772, AMP Deaminase Deficiency

AK1, OMIM *103000, Adenylate Kinase Deficiency

AMPD1, OMIM *102770, Myopathy Due to Myoadenylate Deaminase Deficiency

TPMT, OMIM *187680, Thoipurines, Poor Metabolism of

IMPDH1, OMIM *146690, Retinitis Pigmentosa Type 10, Leber Congenital Amauriosis Type 11

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief summary:

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.

Conditions

AMPD3, OMIM*102772, AMP Deaminase Deficiency

AK1, OMIM *103000, Adenylate Kinase Deficiency

AMPD1, OMIM *102770, Myopathy Due to Myoadenylate Deaminase Deficiency

TPMT, OMIM *187680, Thoipurines, Poor Metabolism of

IMPDH1, OMIM *146690, Retinitis Pigmentosa Type 10, Leber Congenital Amauriosis Type 11

Study ID

NCT06092346

Start date

Dec 19, 2023

Status verified date

Aug 14, 2026

Completion date

Jan 1, 2099

Anticipated

Primary completion date

Jan 1, 2099

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:

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;

  • A medical history that, based on the preponderance of clinical, laboratory, biochemical, and/or genomic evidence is consistent with DPPMs;
  • Clinical findings that can be used to suspect disorders of purine and pyrimidine metabolism will include, but not be limited to the presence of congenital malformations, neurological, behavioral, immunological, rheumatological, hematological, renal involvement; gout; and recurrent rhabdomyolysis in one or more family members.
  • Laboratory findings may include but not limited to elevated CPK (recurrent rhabdomyolysis); neutropenia, lymphopenia, anemia, thrombocytopenia; and immunodeficiency.
  • Biochemical evidence may encompass but not limited to persistent laboratory abnormalities in blood and urinary urate (a terminal product of purine degradation); blood and urinary beta-alanine (a terminal product of pyrimidine degradation); characteristic findings on plasma amino acid profiles (elevated plasma aspartate and glycine); elevated orotic acid on the urine organic acid assay; presence of urate crystals in urine; abnormal findings on the purine and pyrimidine panels (e.g. plasma and urine purines \& pyrimidines biochemical panels at Mayo, PUPYP and PUPYU).
  • Genomic evidence may include the presence of pathogenic and likely pathogenic variants in genes known or plausibly linked to the pathways of the de novo synthesis, degradation, and salvage of purines \& pyrimidines. Participants with variants of unknown significance in the said genes may be invited to participate in the protocol, if they have clinical, laboratory and biochemical evidence consistent with DPPMs.
  • Have a primary metabolic or genetic physician, or primary care provider; and
  • 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.

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:

  • At least one month of age;
  • Relationship either by blood or marriage, to an individual enrolled or about to be enrolled in the study with known DPPM;
  • 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 possible condition; 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.
  • If during the consenting/assenting procedure, review of medical and family history and physical exam, clinical suspicion arises that a family member has symptoms of DPPMs, additional review and/or studies may be recommended to clarify the clinical status.
  • Participants must have a routine clinical care team outside of NIH to enroll in this study.

In order to be eligible to participate in this study as an unrelated healthy volunteer, an individual must meet all the following criteria:

  • No personal or family history of DPPMs;
  • At least one month old;
  • No symptoms of DPPMs;
  • 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;
  • 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.
  • Participants must have a routine clinical care team outside of NIH to enroll in this study.

EXCLUSION CRITERIA:

Individuals meeting the following exclusion criteria are not eligible for the study:

  • Unrelated volunteers who are unaffected with DPPM but have intellectual disability due to other causes, such that they cannot provide informed consent without a guardian/LAR, will not be enrolled in this study. Affected individuals and family member(s) of individuals with DPPM can participate in the study when appropriate informed consent is obtained (with aide of parents/guardian/LAR/bioethics review when necessary).
  • Intercurrent or chronic conditions which in the opinion of the investigators, can then interfere with the interpretation of research studies (e.g. ongoing cancer treatment resulting in bone marrow suppression in a patient with DPPM also presenting with bone marrow suppression).
  • Pregnant participants as unaffected family members or as unrelated healthy volunteers are not able to join the protocol during the pregnancy.
  • Individuals without a routine clinical care team outside of the NIH cannot enroll in this study. We will ask the participants for the name of clinical care team prior to enrollment.

Study Design

Enrollment

999 participants

Anticipated

Interventions and Outcome Measures

Arms

Family Member of a subject with known or suspected DPPM

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.

Healthy Volunteers

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.

Subjects with known or suspected or uncharacterized DPPMs

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.

Primary outcome measure

  • TP describe features of poorly characterized and novel DPPMs. [ Time Frame: indefinite ]

Central Contacts and Locations

Central contacts

Oleg A Shchelochkov, M.D.

(301) 435-2944PurineandPyrimidine@mail.nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

Shannon Haines

240-987-8298shannon.haines@nih.gov

NIH Clinical Center Office of Patient Recruitment (OPR)

(800) 411-1222ccopr@nih.gov

More Information

Sponsor

National Human Genome Research Institute (NHGRI)

Last update posted

Aug 19, 2026

Last verified

Aug 14, 2026

Keywords

  • Pyrimidine and Purine Metabolism Disorders

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-07. This information was provided to ClinicalTrials.gov by National Human Genome Research Institute (NHGRI) on 2026-08-19. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.