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Overview of Purine and Pyrimidine Metabolism Disorders


Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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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.


Purine Metabolism Disorders

Disease (OMIM Number)

Defective Proteins or Enzymes


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

  • Classic form

  • Variant form

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: Supportive care, protective measures, allopurinol, benzodiazepines, certain experimental approaches

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: Allopurinol, anti-inflammatory drugs, colchicines, probenecid, sulfinpyrazone

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*)

  • Type I (severe form)

  • Type II (mild form)

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.

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