Neurologic Manifestations of Xeroderma Pigmentosum Workup

Updated: Mar 19, 2019
  • Author: Peter Hedera, MD, PhD; Chief Editor: Amy Kao, MD  more...
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Laboratory Studies

See the list below:

  • Exclude treatable causes of dementia. Order thyroid function tests, vitamin B-12, erythrocyte sedimentation rate (ESR), and fluorescent treponemal antibody (FTA) in patients with intellectual decline.

  • Screening metabolic studies to investigate developmental delay in children with unequivocal diagnosis of xeroderma pigmentosum have low yields. However, in patients with a less certain diagnosis for xeroderma pigmentosum, consider the following:

    • Metabolic screen

      • Serum and urine amino acids

      • Organic amino acids

      • Lysosomal enzymes

      • Cholesterol esterification assays

      • 24-hour urine copper

      • Urine study for mucopolysaccharides and oligosaccharides

      • Venous lactate and pyruvate

      • Long-chain fatty acids

    • Chromosomal analysis

  • Very-long-chain fatty acids, galactosylceramide beta-galactosidase, and arylsulphatase-A levels can differentiate xeroderma pigmentosum from adrenoleukodystrophy, Krabbe disease, and metachromatic leukodystrophy, respectively.

  • Unscheduled DNA synthesis, UV light survival, complementation studies, and direct DNA testing for mutations are not routinely available (see Pathophysiology). These are performed only on a research basis.


Imaging Studies

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  • Patients with a new onset of ataxia or spastic weakness should undergo neuroimaging, preferably MRI of the brain and spine, to rule out structural abnormalities, including tumors and arteriovenous malformations.

    • Diffuse atrophy of the cerebral cortex and the cerebellum is seen in patients with xeroderma pigmentosum (see images below).

      Axial T2-weighted MRI of the brain of a 47-year-ol Axial T2-weighted MRI of the brain of a 47-year-old woman with xeroderma pigmentosum, complementary group D. She developed progressive ataxia and dementia at age 44 years. Note severe atrophy and normal signal from the white matter.
      Coronal T1-weighted MRI image of the brain of a 47 Coronal T1-weighted MRI image of the brain of a 47-year-old woman who developed progressive ataxia and dementia at age 44 and was found to have xeroderma pigmentosum, complementary group D (see image above). Severe diffuse atrophy involves the brain stem and cerebellum.
    • Some patients may have normal neurologic and cognitive examination in spite of significant cortical atrophy.

    • Patients with a mixed phenotype xeroderma pigmentosum (particularly XP-D) and trichothiodystrophy may have white matter abnormalities (increased signal on T2-weighted images) on MRI of the brain, suggesting demyelination.

  • Basal ganglia calcification can be better assessed by the axial computed tomography (CT).


Other Tests

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  • Electromyography (EMG) and nerve conduction studies (NCS) are helpful because axonal polyneuropathy is common in xeroderma pigmentosum.

  • Perform electroencephalogram (EEG) in patients who develop seizures. Seizures are typically partial complex with secondary generalization. Focal spike and wave discharges may occur in the interictal period. Diffuse background slowing may be present.

  • Use audiogram and brainstem evoked potentials for screening, since the prevalence of hearing loss is high in xeroderma pigmentosum.


Histologic Findings

The few reports of nerve biopsy in patients with xeroderma pigmentosum demonstrated a marked decrease of myelinated fibers. Sural nerve biopsy is not useful for clinical diagnosis/management.