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

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
• 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

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI)

  lead NIH

Principal Investigators

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

Eligibility

Min Age

1 Month

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-19

Primary Completion

2099-01-01

Completion

2099-01-01

Countries

• United States

Study Locations