eMedicine Specialties > Neurology > Pediatric Neurology

Lesch-Nyhan Syndrome: Differential Diagnoses & Workup

Author: H A Jinnah, MD, PhD, Professor, Departments of Neurology and Human Genetics, Emory University
Contributor Information and Disclosures

Updated: Dec 15, 2008

Differential Diagnoses

Cerebral Palsy
Inherited Metabolic Disorders
Mental Retardation

Other Problems to Be Considered

Dystonia
Self-injurious behavior

Workup

Laboratory Studies

  • The gross overproduction of uric acid is often evident in routine blood and urine studies.
    • Uric acid levels in the blood typically are elevated, a helpful clue that can be obtained by routine clinical testing; however, hyperuricemia has many different causes, and some patients with Lesch-Nyhan syndrome have serum uric acid levels in the normal range. As a result, serum uric acid levels do not provide reliable diagnostic information.
    • Urinary uric acid excretion also is increased typically. A 24-hour urine sample typically demonstrates a marked increase over normative values, particularly if corrected for patient weight. However, 24-hour samples are notoriously difficult to collect. Calculation of the urinary uric acid to creatinine value in a spot urine specimen provides an alternative method, though less information is available concerning normative values. Hyperuricosuria is neither sensitive nor specific enough to provide reliable diagnostic information.
  • Definitive diagnosis is obtained most often by measurement of HPRT enzyme activity in blood or tissue. Blood samples often are used, though intact fibroblasts or lymphocytes provide more precise information with prognostic implications.
  • Diagnosis is confirmed by identifying a molecular genetic mutation in the HPRT gene. Molecular genetic diagnosis provides an ideal tool for carrier detection and prenatal screening of at-risk pregnancies.
  • Macrocytic anemia, sometimes profound, is relatively common. Vitamin B-12, folate, and iron results are typically normal.

Imaging Studies

  • Neuroimaging studies of the brain, both CT scan and MRI, generally do not reveal obvious structural malformations or signal changes. They may reveal mild loss of brain volume, but this loss is often so small that it escapes notice in routine imaging studies.
  • Neuroimaging studies of the spinal cord, particularly the cervical portions, may reveal early degenerative joint disease that can damage the spinal cord or emerging nerve roots.

Other Tests

  • Noninvasive imaging studies of the kidneys and other parts of the urogenital system are warranted because of the marked increase in the risk for kidney stones.
    • Any patient who develops flank pain, hematuria, or recurrent urinary tract infections should be evaluated.
    • Some authorities have recommended yearly investigations in all patients, because asymptomatic stones or sludge may silently compromise renal function.
  • Since stones composed of uric acid, oxypurine metabolites, or allopurinol are typically radiolucent, they may be invisible on plain films; however, they are imaged easily by renal ultrasound.

More on Lesch-Nyhan Syndrome

Overview: Lesch-Nyhan Syndrome
Differential Diagnoses & Workup: Lesch-Nyhan Syndrome
Treatment & Medication: Lesch-Nyhan Syndrome
Follow-up: Lesch-Nyhan Syndrome
Multimedia: Lesch-Nyhan Syndrome
References
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References

  1. Alford RL, Redman JB, O'Brien WE, et al. Lesch-Nyhan syndrome: carrier and prenatal diagnosis. Prenat Diagn. Apr 1995;15(4):329-38. [Medline].

  2. Jinnah HA, Friedmann T. Lesch-Nyhan disease and its variants. In: Scriver CR, Sly WS, Childs B, Beaudet AL, et al, eds. The Molecular and Metabolic Bases of Inherited Disease. 6th ed. New York, NY: McGraw-Hill; 2000:Chapter 107.

  3. Jinnah HA, De Gregorio L, Harris JC, et al. The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases. Mutat Res. Oct 2000;463(3):309-26. [Medline].

  4. Jinnah HA, Visser JE, Harris JC, et al. Delineation of the motor disorder of Lesch-Nyhan disease. Brain. May 2006;129(Pt 5):1201-17. [Medline].

  5. Lesch M, Nyhan WL. A familial disorder of uric acid metabolism and central nervous system function. Am J Med. Apr 1964;36:561-70. [Medline].

  6. Nyhan WL, Vuong LU, Broock R. Prenatal diagnosis of Lesch-Nyhan disease. Prenat Diagn. Oct 2003;23(10):807-9. [Medline].

  7. Visser JE, Bar PR, Jinnah HA. Lesch-Nyhan disease and the basal ganglia. Brain Res Brain Res Rev. Apr 2000;32(2-3):449-75. [Medline].

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Further Reading

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Keywords

HPRT deficiency, hypoxanthine-guanine phosphoribosyl transferase, Kelley-Seegmiller syndrome, Lesch-Nyhan disease, overproduction of uric acid, neurologic disability, behavioral problems, hyperuricemia, nephrolithiasis with renal failure, gouty arthritis, tophi, dystonia, choreoathetosis, ballismus, spasticity, hyperreflexia, cognitive dysfunction, aggressive behaviors, impulsive behaviors, self-injurious behavior

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Contributor Information and Disclosures

Author

H A Jinnah, MD, PhD, Professor, Departments of Neurology and Human Genetics, Emory University
H A Jinnah, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, Movement Disorders Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Neurology, Division of Pediatrics, Department of Pediatrics, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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