Purines are key components of cellular energy systems (eg, ATP, NAD), signaling (eg, GTP, cAMP, cGMP), and, along with pyrimidines, RNA and DNA production.
Purines and pyrimidines may be synthesized de novo or recycled by a salvage pathway from normal catabolism.
The end product of complete catabolism of purines is uric acid; catabolism of pyrimidines produces citric acid cycle intermediates.
Purine metabolism disorders (see the table) are categorized as
There are a number of pyrimidine metabolism disorders.
See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism.
Purine Metabolism Disorders
Disease (OMIM Number) | Defective Proteins or Enzymes | Comments |
|---|---|---|
Calcium pyrophosphate arthropathy (chondrocalcinosis-2; 118600*) | Increased nucleoside triphosphate pyrophosphohydrolase | Biochemical profile: Calcium pyrophosphate dihydrate crystals in joints Clinical features: Recurrent episodes of monoarticular or multiarticular arthritis Treatment: No clear treatment |
Lesch-Nyhan syndrome (300322*)
| Hypoxanthine-guanine phosphoribosyltransferase | Biochemical profile: Hyperuricemia, hyperuricosuria Clinical features: Orange sandy crystals in diapers, growth failure, uric acid nephropathy and arthropathy, motor delay, hypotonia, self-injurious behavior, spasticity, hyperreflexia, extrapyramidal signs with choreoathetosis, dysarthria, dysphagia, developmental disabilities, megaloblastic anemia In variant form, no self-injurious behavior Treatment: |
Increased activity of phosphoribosylpyrophosphate synthetase (311850*) | Phosphoribosylpyrophosphate synthetase | Biochemical profile: Hyperuricemia Clinical features: Megaloblastic bone marrow, ataxia, hypotonia, hypertonia, psychomotor delay, polyneuropathy, cardiomyopathy, heart failure, uric acid nephropathy and arthropathy, diabetes mellitus, intracerebral calcification Treatment: |
Phosphoribosylpyrophosphate synthetase I deficiency (311850*) | Phosphoribosylpyrophosphate synthetase | Biochemical profile: Increased urinary orotate, hypouricemia Clinical features: Developmental disabilities, seizures with hypsarrhythmia, megaloblastic bone marrow Treatment: Adrenocorticotropic hormone |
Hereditary xanthinuria | Biochemical profile: Xanthinuria, hypouricemia, hypouricosuria Clinical features: Xanthine stones, nephropathy, myopathy Treatment: High fluid intake; low-purine diet | |
Type I (278300*) | Xanthine dehydrogenase | |
Type II (603592*) | Xanthine dehydrogenase and aldehyde oxidase | |
Adenine phosphoribosyltransferase deficiency (102600*) | Adenine phosphoribosyltransferase | Biochemical profile: Urinary 2,8-dihydroxyadenine Clinical features: Urolithiasis, nephropathy, round yellow-brown urine crystals Treatment: High fluid intake, low-purine diet, avoidance of dietary alkalis, renal transplantation |
Type I | No enzyme activity | |
Type II | Residual enzyme activity | |
Adenosine deaminase | Biochemical profile: Elevated serum adenosine and 2′-deoxyadenosine Clinical features: Growth failure, skeletal changes, recurrent infections, severe combined immunodeficiency, B-cell lymphoma, hemolytic anemia, idiopathic thrombocytopenia, hepatosplenomegaly, mesangial sclerosis Treatment: Supportive care, enzyme replacement, bone marrow or stem cell transplantation, experimental gene therapy | |
Increased adenosine deaminase (102730*) | Adenosine deaminase | Biochemical profile: Mild hyperuricemia Clinical features: Hemolytic anemia with anisopoikilocytosis and stomatocytosis Treatment: Deoxycoformycin |
Purine nucleoside phosphorylase | Biochemical profile: Hypouricemia; hypouricosuria; high serum inosine and guanine; high urinary inosine, 2′-deoxyinosine, and 2′-deodyguanosine Clinical features: Growth failure, cellular immunodeficiency, recurrent infections, hepatosplenomegaly, cerebral vasculitis, spastic diplegia, tetraparesis, ataxia, tremors, hypotonia, hypertonia, developmental disabilities, autoimmune hemolytic anemia, idiopathic thrombocytopenia, lymphoma, lymphosarcoma Treatment: Supportive care, stem cell transplantation | |
Myoadenylate deaminase deficiency (adenosine monophosphate deaminase I; 102770*) | Myoadenylate deaminase | Biochemical profile: No specific change Clinical features: Neonatal weakness and hypotonia; exercise-induced weakness or cramping; after exercise, decreased purine release and low increase in serum ammonia (relative to lactate) Treatment: Ribose or xylitol |
Adenylate kinase deficiency (103000*) | Adenylate kinase | Biochemical profile: No specific change Clinical features: Hemolytic anemia Treatment: Supportive care |
Adenylosuccinase deficiency (103050*)
| Adenylosuccinate lyase | Biochemical profile: Elevated succinyladenosine and succinylaminoimidazole carboxamide ribotides in body fluids Clinical features: Autism, severe psychomotor delay, seizures, growth delay, muscle wasting Treatment: Supportive care, adenine, and ribose |
* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man (OMIM) database. | ||
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Online Mendelian Inheritance in Man (OMIM) database: Complete gene, molecular, and chromosomal location information
