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Xanthinuria Clinical Presentation

  • Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD  more...
Updated: Oct 13, 2015


Symptoms are nonspecific and relate to the underlying pathophysiology and secondary complications. In young children, irritability, vomiting, and failure to thrive may be the presenting symptoms. At any age, the patient may present with gross or microscopic hematuria, pyuria, renal colic, dysuria, urinary frequency, urine incontinence, polyuria, abdominal pain, or symptoms of a urinary tract infection. Joint pain and muscle cramps or muscle pain are symptoms of the arthropathy and myopathy, respectively. Moreover, about two thirds of patients are asymptomatic and present with an incidental finding of extremely low levels of uric acid in the blood.[4]

  • Renal system symptoms are not specific to xanthinuria and are typical of any cause of crystal nephropathy and stone formation.
  • Gross or microscopic hematuria may occur as a result of crystalluria or nephrolithiasis.
  • Renal colic is characterized by sudden onset of severe usually unilateral flank pain that may radiate toward the inguinal area.
    • Nausea and vomiting may accompany the episode.
    • In young children or infants, renal colic may present as irritability or unexplained abdominal pain.
  • Urinary tract infection is a frequent complication of any foreign body in the urinary system.
  • Acute renal failure may be the presenting feature of bilateral obstructing urolithiasis or crystal nephropathy.
  • Passing a urinary stone may be the initial clinical manifestation.
  • Myopathy usually occurs in older patients and is related to accumulation of xanthine. The symptoms may include muscle cramps, pain, or tightness in the hands, legs, or jaw. Muscle pain can follow vigorous exercise.
  • Joint pain and stiffness are features of arthropathy.


See the list below:

  • No specific physical examination findings lead to the diagnosis of xanthinuria.
  • Failure to thrive, recurrent emesis, and irritability are nonspecific findings in young children with renal failure or urolithiasis.
  • Fever, flank pain, dysuria, urinary frequency, and urinary urgency are features of a urinary tract infection, which can accompany xanthinuria.
  • Renal colic is a common presenting feature of urolithiasis.
  • Hematuria is a typical feature of urolithiasis and crystalluria.


See the list below:

  • Genetic causes
    • Classic xanthinuria types I and II are autosomal recessive inherited conditions that result in dysfunction of the enzyme xanthine dehydrogenase.
    • Xanthine dehydrogenase catalyzes 2 reactions, conversion of hypoxanthine to xanthine and conversion of xanthine to uric acid.
    • The accumulation of xanthine is caused by the catabolism of guanine to xanthine by guanase and the lack of a salvage pathway for xanthine.
    • Hypoxanthine does not accumulate appreciably because it is efficiently metabolized through a salvage pathway.
  • Iatrogenic causes
    • Allopurinol is administered to block xanthine dehydrogenase and prevent uric acid overproduction, which leads to the accumulation of xanthine. Rarely, in the setting of aggressive chemotherapy with rapid tumor lysis and allopurinol therapy, patients can develop complications of renal failure from xanthine crystal nephropathy. Volume depletion may also be involved.
    • In complete HGPRT deficiency (ie, Lesch-Nyhan syndrome) or in partial deficiency of HGPRT, an overproduction of uric acid occurs. Allopurinol is administered to reduce uric acid production, and this leads to xanthine and hypoxanthine accumulation. Hypoxanthine accumulates because HGPRT is the enzyme for the hypoxanthine salvage pathway.
Contributor Information and Disclosures

Sahar Fathallah-Shaykh, MD Associate Professor of Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.


Steven C Diven, MD Medical Director of Pediatric Dialysis Unit, Assistant Professor, Department of Pediatrics, University of Texas Medical Branch at Galveston

Steven C Diven, MD is a member of the following medical societies: National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Luther Travis, MD Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine

Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, Texas Pediatric Society

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Additional Contributors

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical and Dental Associations, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, Southwest Pediatric Nephrology Study Group

Disclosure: Nothing to disclose.

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Purine metabolic pathway.
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