Xanthinuria Clinical Presentation

  • Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD   more...
 
Updated: Jun 28, 2011
 

History

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.

  • 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.
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Physical

  • 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.
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Causes

  • 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.
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Contributor Information and Disclosures
Author

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

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

Disclosure: emedecine Honoraria Other

Coauthor(s)

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

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 & Dental Society, 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, and Southwest Pediatric Nephrology Study Group

Disclosure: The Osler Institute Honoraria Speaking and teaching

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, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

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, Children's Memorial Hospital

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

Disclosure: Merck Grant/research funds None; NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

References

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  2. Cameron JS, Moro F, Simmonds HA. Gout, uric acid and purine metabolism in paediatric nephrology. Pediatr Nephrol. Feb 1993;7(1):105-18. [Medline].

  3. Carpenter TO, Lebowitz RL, Nelson D, Bauer S. Hereditary xanthinuria presenting in infancy with nephrolithiasis. J Pediatr. Aug 1986;109(2):307-9. [Medline].

  4. Fildes RD. Hereditary xanthinuria with severe urolithiasis occurring in infancy as renal tubular acidosis and hypercalciuria. J Pediatr. Aug 1989;115(2):277-80. [Medline].

  5. Gomez GA, Stutzman L, Chu TM. Xanthine nephropathy during chemotherapy in deficiency of hypoxanthine- guanine phosphoribosyltransferase. Arch Intern Med. Jun 1978;138(6):1017-9. [Medline].

  6. Leimkuhler S, Charcosset M, Latour P, et al. Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase. Hum Genet. 2005;117(6):565-70. [Medline].

  7. Macaya A, Brunso L, Fernandez-Castillo N, et al. Molybdenum cofactor deficiency presenting as neonatal hyperekplexia: a clinical, biochemical and genetic study. Neuropediatrics.Dec;. 2005;36(6):389-94. [Medline].

  8. Reiter S, Simmonds HA, Zollner N, et al. Demonstration of a combined deficiency of xanthine oxidase and aldehyde oxidase in xanthinuric patients not forming oxipurinol. Clin Chim Acta. Mar 15 1990;187(3):221-34. [Medline].

  9. Simmonds HA, Reiter S, Nishino T. Hereditary xanthinuria. In: The Metabolic and Molecular Bases of Inherited Disease. 1995:1781-97.

  10. Teksam O, Yurdakok M, Coskun T. Molybdenum cofactor deficiency presenting with severe metabolic acidosis and intracranial hemorrhage. J Child Neurol. 2005;20(2):155-7. [Medline].

  11. van Gennip AH, Mandel H, Stroomer LEM. Effects of allopurinol on the xanthinuria in a patient with molybdenum cofactor deficiency. In: Purine and Pyrimidine Metabolism in Man. Vol 8. 1995:375-8.

  12. Zannolli R, Micheli V, Mazzei MA, et al. Hereditary xanthinuria type II associated with mental delay, autism, cortical renal cysts, nephrocalcinosis, osteopenia, and hair and teeth defects. J Med Genet. Nov 2003;40(11):e121. [Medline].

 
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