eMedicine Specialties > Neurology > Pediatric Neurology

Xeroderma Pigmentosum: Differential Diagnoses & Workup

Author: Peter Hedera, MD, Assistant Professor, Department of Neurology, Vanderbilt University
Contributor Information and Disclosures

Updated: Jan 8, 2009

Differential Diagnoses

Chorea in Adults
Multiple Sclerosis
Cortical Basal Ganglionic Degeneration
Multiple System Atrophy
Diabetic Neuropathy
Olivopontocerebellar Atrophy
Frontal and Temporal Lobe Dementia
Parkinson-Plus Syndromes
Glioblastoma Multiforme
Thyroid Disease
Hallervorden-Spatz Disease
Vitamin B-12 Associated Neurological Diseases
Inherited Metabolic Disorders
Mental Retardation

Other Problems to Be Considered

Cockayne syndrome
Dementia of other causes
Developmental delay of other causes
Metabolic disorders
Trichothiodystrophy
Werner syndrome

Workup

Laboratory Studies

  • 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

  • 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 Media files 3-4).
    • 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

  • 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.

More on Xeroderma Pigmentosum

Overview: Xeroderma Pigmentosum
Differential Diagnoses & Workup: Xeroderma Pigmentosum
Treatment & Medication: Xeroderma Pigmentosum
Follow-up: Xeroderma Pigmentosum
Multimedia: Xeroderma Pigmentosum
References
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References

  1. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. Arch Dermatol. Feb 1987;123(2):241-50. [Medline].

  2. Mimaki T, Itoh N, Abe J, et al. Neurological manifestations in xeroderma pigmentosum. Ann Neurol. Jul 1986;20(1):70-5. [Medline].

  3. Anttinen A, Koulu L, Nikoskelainen E, Portin R, Kurki T, Erkinjuntti M, et al. Neurological symptoms and natural course of xeroderma pigmentosum. Brain. Aug 2008;131:1979-89. [Medline].

  4. Jaspers NG, Raams A, Silengo MC, Wijgers N, Niedernhofer LJ, Robinson AR, et al. First reported patient with human ERCC1 deficiency has cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure. Am J Hum Genet. Mar 2007;80(3):457-66. [Medline].

  5. Cleaver JE. Defective repair replication of DNA in xeroderma pigmentosum. Nature. May 18 1968;218(5142):652-6. [Medline].

  6. De Sanctinis C, Cacchione A. L'idiozia xerodermica. Riv Sepr Freniatr. 1932;56:269-292.

  7. Hakamada S, Watanabe K, Sobue G, et al. Xeroderma pigmentosum: neurological, neurophysiological and morphological studies. Eur Neurol. 1982;21(2):69-76. [Medline].

  8. Hayashi M, Araki S, Kohyama J, et al. Oxidative nucleotide damage and superoxide dismutase expression in the brains of xeroderma pigmentosum group A and Cockayne syndrome. Brain Dev. Jan 2005;27(1):34-8. [Medline].

  9. Johnson RT, Squires S. The XPD complementation group. Insights into xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy. Mutat Res. Mar 1992;273(2):97-118. [Medline].

  10. Kohyama J, Furushima W, Sugawara Y, et al. Convulsive episodes in patients with group A xeroderma pigmentosum. Acta Neurol Scand. Oct 2005;112(4):265-9. [Medline].

  11. Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie. Nov 2003;85(11):1101-11. [Medline].

  12. Mimaki T, Tagawa T, Tanaka J, et al. EEG and CT abnormalities in xeroderma pigmentosum. Acta Neurol Scand. Aug 1989;80(2):136-41. [Medline].

  13. Moriwaki S, Nishigori C, Imamura S, et al. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Dermatol. Jan 1993;128(1):91-4. [Medline].

  14. Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. Jan 1 1992;42(1):68-84. [Medline].

  15. Rapin I, Weidenheim K, Lindenbaum Y, et al. Cockayne syndrome in adults: review with clinical and pathologic study of a new case. J Child Neurol. Nov 2006;21(11):991-1006. [Medline].

  16. Robbins JH, Brumback RA, Mendiones M, et al. Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Brain. Jun 1991;114 ( Pt 3):1335-61. [Medline].

  17. Robbins JH, Brumback RA, Moshell AN. Clinically asymptomatic xeroderma pigmentosum neurological disease in an adult: evidence for a neurodegeneration in later life caused by defective DNA repair. Eur Neurol. 1993;33(3):188-90. [Medline].

  18. Robbins JH, Kraemer KH, Lutzner MA, et al. Xeroderma pigmentosum. An inherited diseases with sun sensitivity, multiple cutaneous neoplasms, and abnormal DNA repair. Ann Intern Med. Feb 1974;80(2):221-48. [Medline].

  19. Roytta M, Anttinen A. Xeroderma pigmentosum with neurological abnormalities. A clinical and neuropathological study. Acta Neurol Scand. Feb 1986;73(2):191-9. [Medline].

  20. Weeda G, Ma LB, van Ham RC, et al. Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome. Nucleic Acids Res. Nov 25 1991;19(22):6301-8. [Medline].

  21. Weeda G, van Ham RC, Vermeulen W, et al. A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome. Cell. Aug 24 1990;62(4):777-91. [Medline].

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Further Reading

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Keywords

XP, De Sanctis-Cacchione syndrome, sensitivity to ultraviolet light, light sensitivity, skin cancer, abnormal skin pigmentation, Cockayne syndrome, CS

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Contributor Information and Disclosures

Author

Peter Hedera, MD, Assistant Professor, Department of Neurology, Vanderbilt University
Peter Hedera, MD is a member of the following medical societies: American Academy of Neurology, American College of Medical Genetics, and American Neurological Association
Disclosure: Nothing to disclose.

Medical Editor

Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research
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

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Neurology, Division of Pediatric Neurology, 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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