Clinical Guidance

In the wide and continuous spectrum of clinical manifestations associated with PRPS1 missense variants that result in a loss of function, a relationship between the type (location) of disruption of the PRS-I enzyme and phenotype has been suggested. The most severe phenotypes are caused by variants that are predicted to affect allosteric and active sites, and the milder phenotypes are caused by variants that are predicted to disrupt the structure locally . In females, who predictably have less severe manifestations, the ratio of X-chromosome inactivation adds an additional variable in predicting clinical outcome .

Diagnostic Criteria

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care . No consensus clinical diagnostic criteria for phosphoribosylpyrophosphate synthetase (PRS) deficiency have been published.

Suggestive Findings

PRS deficiency should be suspected in a male proband with the following clinical and supportive laboratory findings and family history.

Clinical findings in males

Management Guidelines

No clinical practice guidelines for phosphoribosylpyrophosphate synthetase (PRS) deficiency have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with PRS deficiency, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 2. PRS Deficiency: Recommended Evaluations Following Initial Diagnosis

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations listed in are recommended. Table 4. PRS Deficiency: Recommended Surveillance