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Genetics Home Reference: your guide to understanding genetic conditions
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Phosphoribosylpyrophosphate synthetase superactivity

(often shortened to PRS superactivity)
Reviewed September 2009

What is PRS superactivity?

Phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) is characterized by the overproduction and accumulation of uric acid (a waste product of normal chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which is arthritis caused by an accumulation of uric acid crystals in the joints. Individuals with PRS superactivity also develop kidney or bladder stones that may result in episodes of acute kidney failure.

There are two forms of PRS superactivity, a severe form that begins in infancy or early childhood, and a milder form that typically appears in late adolescence or early adulthood. In both forms, a kidney or bladder stone is often the first symptom. Gout and impairment of kidney function may develop if the condition is not adequately controlled with medication and dietary restrictions. People with the severe form may also have neurological problems, including hearing loss caused by changes in the inner ear (sensorineural hearing loss), weak muscle tone (hypotonia), impaired muscle coordination (ataxia), and developmental delay.

How common is PRS superactivity?

PRS superactivity is believed to be a rare disorder. Approximately 30 families with the condition have been reported. More than two thirds of these families are affected by the milder form of the disease.

What genes are related to PRS superactivity?

Certain mutations in the PRPS1 gene cause PRS superactivity. The PRPS1 gene provides instructions for making an enzyme called phosphoribosyl pyrophosphate synthetase 1, or PRPP synthetase 1. This enzyme helps produce a molecule called phosphoribosyl pyrophosphate (PRPP). PRPP is involved in producing purine and pyrimidine nucleotides. These nucleotides are building blocks of DNA, its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in the cell. PRPP synthetase 1 and PRPP also play a key role in recycling purines from the breakdown of DNA and RNA, a faster and more efficient way of making purines available.

In people with the more severe form of PRS superactivity, PRPS1 gene mutations change single protein building blocks (amino acids) in the PRPP synthetase 1 enzyme, resulting in a poorly regulated, overactive enzyme. In the milder form of PRS superactivity, the PRPS1 gene is overactive for reasons that are not well understood. PRPS1 gene overactivity increases the production of normal PRPP synthetase 1 enzyme, which increases the availability of PRPP. In both forms of the disorder, excessive amounts of purines are generated.

Under these conditions, uric acid, a waste product of purine breakdown, accumulates in the body. A buildup of uric acid crystals can cause gout, kidney stones, and bladder stones. It is unclear how PRPS1 gene mutations are related to the neurological problems associated with the severe form of PRS superactivity.

Related Gene(s)

Changes in this gene are associated with phosphoribosylpyrophosphate synthetase superactivity.

  • PRPS1

How do people inherit PRS superactivity?

This condition is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell sometimes causes the disorder.

In most reported cases, affected individuals have inherited the mutation from a parent who carries an altered copy of the PRPS1 gene. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. PRS superactivity may also result from new mutations in the PRPS1 gene and can occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of PRS superactivity?

These resources address the diagnosis or management of PRS superactivity and may include treatment providers.

  • Gene Review: Phosphoribosylpyrophosphate Synthetase Superactivity (http://www.ncbi.nlm.nih.gov/books/NBK1973)
  • Genetic Testing Registry: Phosphoribosylpyrophosphate synthetase superactivity (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1970827)
  • MedlinePlus Encyclopedia: Hearing Loss (http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm)
  • MedlinePlus Encyclopedia: Movement, Uncoordinated (http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm)

You might also find information on the diagnosis or management of PRS superactivity in Educational resources (http://www.ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/phosphoribosylpyrophosphate-synthetase-superactivity/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about PRS superactivity?

You may find the following resources about PRS superactivity helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for PRS superactivity?

  • gout, PRPS-related
  • PRPP synthetase overactivity
  • PRPP synthetase superactivity
  • PRPS1 superactivity
  • PRS overactivity

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about PRS superactivity?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding PRS superactivity?

acids ; acute ; arthritis ; ataxia ; ATP ; breakdown ; cell ; chromosome ; developmental delay ; DNA ; enzyme ; gene ; gout ; GTP ; hypotonia ; inheritance ; inherited ; kidney ; kidney stones ; molecule ; muscle tone ; mutation ; neurological ; protein ; purines ; RNA ; sensorineural ; sensorineural hearing loss ; sex chromosomes ; stone ; symptom ; uric acid

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ahmed M, Taylor W, Smith PR, Becker MA. Accelerated transcription of PRPS1 in X-linked overactivity of normal human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1999 Mar 12;274(11):7482-8. (http://www.ncbi.nlm.nih.gov/pubmed/10066814?dopt=Abstract)
  • Becker MA, Smith PR, Taylor W, Mustafi R, Switzer RL. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest. 1995 Nov;96(5):2133-41. (http://www.ncbi.nlm.nih.gov/pubmed/7593598?dopt=Abstract)
  • Becker MA, Taylor W, Smith PR, Ahmed M. Overexpression of the normal phosphoribosylpyrophosphate synthetase 1 isoform underlies catalytic superactivity of human phosphoribosylpyrophosphate synthetase. J Biol Chem. 1996 Aug 16;271(33):19894-9. (http://www.ncbi.nlm.nih.gov/pubmed/8702702?dopt=Abstract)
  • García-Pavía P, Torres RJ, Rivero M, Ahmed M, García-Puig J, Becker MA. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis Rheum. 2003 Jul;48(7):2036-41. (http://www.ncbi.nlm.nih.gov/pubmed/12847698?dopt=Abstract)
  • Gene Review: Phosphoribosylpyrophosphate Synthetase Superactivity (http://www.ncbi.nlm.nih.gov/books/NBK1973)
  • Nyhan WL. Disorders of purine and pyrimidine metabolism. Mol Genet Metab. 2005 Sep-Oct;86(1-2):25-33. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16176880?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: September 2009
Published: November 24, 2014