Phosphoribosylpyrophosphate synthetase deficiency

Phosphoribosylpyrophosphate synthetase deficiency (PRPS deficiency) is a rare genetic disorder characterized by a deficiency in the enzyme phosphoribosylpyrophosphate synthetase (PRPS). This enzyme plays a critical role in the purine and pyrimidine synthesis pathways, which are essential for DNA and RNA synthesis. The deficiency leads to various clinical manifestations, including gout, uric acid kidney stones, neurodevelopmental disorders, and in some cases, sensorineural hearing loss.

Causes

Phosphoribosylpyrophosphate synthetase deficiency is caused by mutations in the PRPS1 gene, which encodes the PRPS enzyme. These mutations lead to either a loss of function or a gain of function of the enzyme, disrupting the balance of purine synthesis. The condition is inherited in an X-linked recessive manner, meaning it predominantly affects males, while females can be carriers of the condition.

Symptoms

The symptoms of PRPS deficiency can vary widely among affected individuals. Common symptoms include:

• Gout: The accumulation of uric acid in the joints, causing painful swelling.
• Uric acid kidney stones: The formation of kidney stones due to high levels of uric acid in the urine.
• Neurodevelopmental disorders: Delays in development, intellectual disability, and behavioral problems.
• Sensorineural hearing loss: A type of hearing loss resulting from damage to the inner ear or the nerve pathways from the inner ear to the brain.

Diagnosis

Diagnosis of PRPS deficiency involves a combination of clinical evaluation, family history, and genetic testing. Measurement of PRPS enzyme activity in red blood cells or fibroblasts can also aid in the diagnosis. Genetic testing is crucial for identifying mutations in the PRPS1 gene.

Treatment

There is no cure for PRPS deficiency, and treatment focuses on managing symptoms and preventing complications. Treatment options may include:

• Medications to control uric acid levels, such as allopurinol or febuxostat, to prevent gout and kidney stones.
• Supportive therapies for neurodevelopmental disorders, including physical therapy, occupational therapy, and speech therapy.
• Hearing aids or cochlear implants for those with sensorineural hearing loss.

Prognosis

The prognosis for individuals with PRPS deficiency varies depending on the severity of symptoms and the effectiveness of management strategies. Early diagnosis and treatment can improve the quality of life and reduce the risk of complications.

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