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Purine Catabolism 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.

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

Diagnosis is suspected clinically and typically confirmed by DNA analysis. See also Approach to the Patient With a Suspected Inherited Disorder of Metabolism and testing for suspected inherited disorders of metabolism.

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.

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 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.

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