Purine and Pyrimidine Metabolic diseases

Background

Purines are the source of our energy, adenosine triphosphate (ATP), and with pyrimidines are the building blocks of our DNA. Their production, recycling and breakdown involves a number of steps, each catalysed by a different enzyme. These rare disorders result when one of these enzymes is deficient. To date, 27 enzyme deficiencies have been described, but some appear relatively benign with no obvious clinical problems or symptoms.

Credits

Medical text written October 2002 by Dr M Champion. Last reviewed February 2020 Dr M Champion, Consultant in Paediatric Inherited Metabolic Medicine, Evelina Children’s Hospital, London, UK.

What are the symptoms?

For those purine and pyrimidine disorders that do present with symptoms, almost any system can be affected. Particular problems include kidney stones and renal disease (see entry Kidney disease), recurrent infections and severe immune deficiency, severe recurrent anaemia (anemia – US), muscle cramps and wasting, arthritis, neurological problems such as developmental delay, autism (see entry Autism Spectrum conditions) and seizures (see entry Epilepsy). They may also be responsible for adverse reactions to chemotherapy in patients undergoing treatment for cancer. Although originally thought to be childhood problems, it is clear that they may present at any age.

Symptoms may be severe and life-threatening.

How is it treated?

Specific treatment is only available for a small number of these conditions at present.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
The mode of inheritance of these disorders is autosomal recessive, except Lesch Nyhan syndrome (HPRT deficiency) and phosphoribosylpyrophosphatesynthetase superactivity (PRPS) which are X-linked conditions, and familial juvenile hyperuricaemic nephropathy which is dominant. The degree of severity may be highly variable, even within the same family.

Prenatal diagnosis
Prenatal diagnosis is available for some of the purine and pyrimidine disorders.

Is there support?

Information and support in the UK for Purine and Pyrimidine Metabolic diseases is available from Metabolic Support UK (see entry Inherited Metabolic diseases).

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