RECRUITING

A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders

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Conditions

AMPD3, OMIM*102772, AMP Deaminase DeficiencyAK1, OMIM *103000, Adenylate Kinase DeficiencyAMPD1, OMIM *102770, Myopathy Due to Myoadenylate Deaminase DeficiencyTPMT, OMIM *187680, Thoipurines, Poor Metabolism ofIMPDH1, OMIM *146690, Retinitis Pigmentosa Type 10, Leber Congenital Amauriosis Type 11APRT, OMIM *102600, Adenine Phosphoribosyltransferase DeficiencyHPRT1, OMIM *308000 Lesch-Nyhan DiseaseXDH, OMIM *607633, Xanthinuria Type 1SLC2A9, OMIM *606142 HypouricemiaSLC22A12, OMIM *607096 HypouricemiaPRPS1 Def, OMIM *311850, Arts Syndrome; Charcot-Marie-Tooth DiseasePRPS1 SA, OMIM *311850 Gout, PRPS-related Phosphoribosylpyrophosphate Synthetase SuperactivityAMPD2, OMIM *102771, Spastic Paraplegia 63; Pontocerebellar HypoplasiaITPA, OMIM *147520, Inosine Triphosphatase Deficiency; Developmental and Epileptic Encephalopathy 35ADSL, OMIM *608222, Adenylosuccinate Lyase DeficiencyPNP, OMIM *164050, Nucleoside Phosphorylase DeficiencyADA2, OMIM *607575,Sneddon Syndrome; VAIHSCAD, *1140120, Developmental and Epileptic EncephalopathyUPB1, OMIM *606673, Beta-ureidopropionase DeficiencyDPYS, OMIM *613326, Dihydropyrimidinase DeficiencyDPYD, OMIM *274270, Dihydropyrimidine Dehydrogenase DeficiencyDHODH, OMIM *126064, Miller Syndrome (Postaxial Acrofacial Dysostosis)UMPS, OMIM *613891, Orotic AciduriaNT5C3A<TAB>, OMIM *606224, Anemia, Hemolytic, Due to UMPH1 DeficiencyUNG, OMIM *191525, Hyper-IgM Syndrome 5AICDA, OMIM *605257, Immunodeficiency With Hyper-IgM, Type 2; HIGM2Purine-Pyrimidine MetabolismMetabolic DiseasePyrimidine and Purine Metabolism Disorders

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Prospective Study of the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders

Quick Facts

Study Start:2023-12-19
Study Completion:2099-01-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06092346

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Month to 100 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * At least one month of age;
  2. * A medical history that, based on the preponderance of clinical, laboratory, biochemical, and/or genomic evidence is consistent with DPPMs;
  3. * 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.
  4. * Laboratory findings may include but not limited to elevated CPK (recurrent rhabdomyolysis); neutropenia, lymphopenia, anemia, thrombocytopenia; and immunodeficiency.
  5. * 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).
  6. * 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.
  7. * Have a primary metabolic or genetic physician, or primary care provider; and
  8. * 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.
  9. * At least one month of age;
  10. * Relationship either by blood or marriage, to an individual enrolled or about to be enrolled in the study with known DPPM;
  11. * 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
  12. * 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.
  13. * 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.
  14. * Participants must have a routine clinical care team outside of NIH to enroll in this study.
  15. * No personal or family history of DPPMs;
  16. * At least one month old;
  17. * No symptoms of DPPMs;
  18. * 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;
  19. * 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.
  20. * Participants must have a routine clinical care team outside of NIH to enroll in this study.
  1. * 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).
  2. * 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).
  3. * Pregnant participants as unaffected family members or as unrelated healthy volunteers are not able to join the protocol during the pregnancy.
  4. * 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.

Contacts and Locations

Study Contact

Oleg A Shchelochkov, M.D.
CONTACT
(301) 435-2944
PurineandPyrimidine@mail.nih.gov

Principal Investigator

Oleg A Shchelochkov, M.D.
PRINCIPAL_INVESTIGATOR
National Human Genome Research Institute (NHGRI)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Human Genome Research Institute (NHGRI)

  • Oleg A Shchelochkov, M.D., PRINCIPAL_INVESTIGATOR, National Human Genome Research Institute (NHGRI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-19
Study Completion Date2099-01-01

Study Record Updates

Study Start Date2023-12-19
Study Completion Date2099-01-01

Terms related to this study

Keywords Provided by Researchers

  • Pyrimidine and Purine Metabolism Disorders

Additional Relevant MeSH Terms

  • 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
  • APRT, OMIM *102600, Adenine Phosphoribosyltransferase Deficiency
  • HPRT1, OMIM *308000 Lesch-Nyhan Disease
  • XDH, OMIM *607633, Xanthinuria Type 1
  • SLC2A9, OMIM *606142 Hypouricemia
  • SLC22A12, OMIM *607096 Hypouricemia
  • PRPS1 Def, OMIM *311850, Arts Syndrome; Charcot-Marie-Tooth Disease
  • PRPS1 SA, OMIM *311850 Gout, PRPS-related Phosphoribosylpyrophosphate Synthetase Superactivity
  • AMPD2, OMIM *102771, Spastic Paraplegia 63; Pontocerebellar Hypoplasia
  • ITPA, OMIM *147520, Inosine Triphosphatase Deficiency; Developmental and Epileptic Encephalopathy 35
  • ADSL, OMIM *608222, Adenylosuccinate Lyase Deficiency
  • PNP, OMIM *164050, Nucleoside Phosphorylase Deficiency
  • ADA2, OMIM *607575,Sneddon Syndrome; VAIHS
  • CAD, *1140120, Developmental and Epileptic Encephalopathy
  • UPB1, OMIM *606673, Beta-ureidopropionase Deficiency
  • DPYS, OMIM *613326, Dihydropyrimidinase Deficiency
  • DPYD, OMIM *274270, Dihydropyrimidine Dehydrogenase Deficiency
  • DHODH, OMIM *126064, Miller Syndrome (Postaxial Acrofacial Dysostosis)
  • UMPS, OMIM *613891, Orotic Aciduria
  • NT5C3A<TAB>, OMIM *606224, Anemia, Hemolytic, Due to UMPH1 Deficiency
  • UNG, OMIM *191525, Hyper-IgM Syndrome 5
  • AICDA, OMIM *605257, Immunodeficiency With Hyper-IgM, Type 2; HIGM2
  • Purine-Pyrimidine Metabolism
  • Metabolic Disease