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Lesch-Nyhan Disease Workup

  • Author: H A Jinnah, MD, PhD; Chief Editor: Amy Kao, MD  more...
Updated: Dec 14, 2015

Approach Considerations

In patients with Lesch-Nyhan disease, uric acid levels in the blood and urine are typically, but not always, increased. Definitive diagnosis is generally obtained by measurement of the hypoxanthine-guanine phosphoribosyl transferase (HPRT) enzyme. Confirmation of the diagnosis is most reliably made by identification of the HPRT1 gene.


Lab Studies

The gross overproduction of uric acid is often evident in routine blood and urine studies.[2] 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 disease have serum uric acid levels in the normal range. As a result, serum uric acid levels do not provide reliable diagnostic information.

A 24-hour urine sample typically demonstrates a marked increase of uric acid over normative values, particularly if corrected for patient weight. However, 24-hour samples are notoriously difficult to collect. Calculation of the concentration ratio of urinary uric acid to creatinine in a spot urine specimen provides an alternative method, though less information is available concerning normative values. Hyperuricosuria is neither sensitive enough 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 levels are typically normal.


Imaging Studies

Neuroimaging studies of the brain, by CT scan and MRI, generally do not reveal obvious structural malformations or signal changes in patients with Lesch-Nyhan disease.[3] They may reveal mild loss of brain volume, but this loss is often so small that it escapes notice in routine imaging studies. Quantitative MRI measurements reveal significant loss of brain volume in the basal ganglia and frontal cortex, sparing the occipital lobes and cerebellum.[12]

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.

Noninvasive imaging studies of the kidneys and other parts of the urogenital system are warranted because of the marked increase in the risk of 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 ultrasonography.

Contributor Information and Disclosures

H A Jinnah, MD, PhD Professor, Departments of Neurology, Human Genetics, and Pediatrics, Emory University School of Medicine

H A Jinnah, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, International Parkinson and Movement Disorder Society, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.


Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, and Child Neurology Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

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The HPRT gene has 9 exons, with the coding region depicted as light gray boxes. Genetic mutations in Lesch-Nyhan disease and its variants are heterogenous and include point mutations leading to amino acid substitution (yellow circles), point mutations leading to premature stop (red squares), insertions (blue triangles), deletions (white lines), and other more complex changes (not shown).
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