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Purine Catabolism Disorders


Matt Demczko

, MD, Mitochondrial Medicine, Children's Hospital of Philadelphia

Reviewed/Revised Oct 2021 | Modified Nov 2021

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.

In addition to purine catabolism disorders, purine metabolism disorders (see also table Purine Metabolism Disorders Purine Metabolism Disorders Purine Metabolism Disorders ) include

Myoadenylate deaminase deficiency (or muscle adenosine monophosphate deaminase deficiency)

The enzyme myoadenylate deaminase converts AMP to inosine and ammonia. Deficiency may be asymptomatic or it may cause exercise-induced myalgias or cramping; expression seems to be variable because, despite the high frequency of the mutant allele (10 to 14%), the frequency of the muscle phenotype is quite low in patients homozygous for the mutant allele. When symptomatic patients exercise, they do not accumulate ammonia or inosine monophosphate as do unaffected people; this is how the disorder is diagnosed.

Treatment of myoadenylate deaminase deficiency is exercise modulation as appropriate.

Adenosine deaminase deficiency

Adenosine deaminase converts adenosine and deoxyadenosine to inosine and deoxyinosine, which are further broken down and excreted. Enzyme deficiency (from 1 of > 60 known mutations) results in accumulation of adenosine, which is converted to its ribonucleotide and deoxyribonucleotide (dATP) forms by cellular kinases. The dATP increase results in inhibition of ribonucleotide reductase and underproduction of other deoxyribonucleotides. DNA replication is compromised as a result. Immune cells are especially sensitive to this defect; adenosine deaminase deficiency causes one form of severe combined immunodeficiency Severe Combined Immunodeficiency (SCID) Severe combined immunodeficiency is characterized by low to absent T cells and a low, high, or normal number of B cells and natural killer cells. Most infants develop opportunistic infections... read more .

Diagnosis of adenosine deaminase deficiency is by DNA analysis.

Treatment of adenosine deaminase deficiency is by bone marrow or stem cell transplantation and enzyme replacement therapy. Somatic cell gene therapy is being evaluated as well.

Purine nucleoside phosphorylase deficiency

This rare, autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more deficiency is characterized by immunodeficiency with severe T-cell dysfunction and often neurologic symptoms. Manifestations are lymphopenia, thymic deficiency, recurrent infections, and hypouricemia. Many patients have developmental delay, ataxia, or spasticity.

Diagnosis of purine nucleoside phosphorylase deficiency is by DNA analysis.

Treatment of purine nucleoside phosphorylase deficiency is with bone marrow or stem cell transplantation.

Xanthine oxidase deficiency

Xanthine oxidase is the enzyme that catalyzes uric acid production from xanthine and hypoxanthine. Deficiency causes buildup of xanthine, which may precipitate in the urine, causing symptomatic stones with hematuria, urinary colic, and urinary tract infections.

Diagnosis of xanthine oxidase deficiency is by DNA analysis. Enzyme determination requires liver or intestinal mucosal biopsy and is rarely indicated.

Treatment of xanthine oxidase deficiency is high fluid intake to minimize likelihood of stone formation and allopurinol in some patients.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Drug Name Select Trade
Adenocard, Adenoscan
Aloprim, Zyloprim
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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