Kearns-Sayre Syndrome Workup

  • Author: Anna Purna Basu, PhD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Feb 4, 2010
 

Laboratory Studies

The following studies are indicated in Kearns-Sayre syndrome (KSS):

  • Urine measurements of pH, protein, glucose, and amino acid levels are indicated.
  • Serum creatinine kinase level may be within the reference range or moderately elevated.
  • Blood lactate and pyruvate are usually elevated. Cerebrospinal fluid (CSF) lactate levels are elevated even if blood lactate levels are within the reference range.[10] CSF protein levels are very frequently elevated.
  • In young children, single large-scale deletions may be detectable in blood. Alternatively, diagnosis may be established by muscle biopsy with histochemistry and mtDNA analysis for major rearrangements.[11]
  • Screening is recommended to exclude the endocrinologic abnormalities that occur in many patients.[12] Measure serum electrolyte, glucose, calcium, magnesium, and plasma cortisol levels as well as thyroid function.
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Imaging Studies

  • MRI of the brain may reveal subcortical white matter lesions (hyperintense on T2 and fluid attenuation inversion recovery [FLAIR], may be bilateral) along with involvement of thalamus, basal ganglia, and brainstem.
  • Cerebral and cerebellar atrophy may be present.[13, 14]
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Other Tests

  • ECG reveals cardiac conduction defects; measurement of the PR interval is indicated.[15]
  • Echocardiography is used to look for cardiomyopathy.
  • Electroretinography helps assess retinal degeneration.
  • Audiometry helps detect sensorineural deafness.
  • Electroencephalography during period of encephalopathy reveals generalized slow wave activity.
  • Electromyography and nerve conduction findings may be normal or may show mild myopathy with or without neuropathy.
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Procedures

  • Perform a lumbar puncture and measure protein and lactate levels in the CSF.
  • Muscle biopsy may reveal ragged red fibers (as is shown in the image below).Modified Gomori Trichrome stain showing ragged redModified Gomori Trichrome stain showing ragged red fibres. These show red staining round the periphery as well as within the sarcoplasm, giving a speckled appearance. Of the two affected muscle fibres pictured here, the one on the right shows a more extreme degree of mitochondrial proliferation and also some degeneration/vacuolation than the one on the left.
  • Muscle histochemistry (as is shown in the image below) reveals deficiency of cytochrome c oxidase.Skeletal muscle stained for both cytochrome oxidasSkeletal muscle stained for both cytochrome oxidase (COX) and succinic dehydrogenase (SDH), two mitochondrial respiratory chain enzymes. Fibers that stain only for SDH and are COX-negative appear blue. Original magnification X 50.
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Histologic Findings

  • In patients with Kearns-Sayre syndrome, as with other mitochondrial encephalopathies, spongy degenerative changes occur in both the gray and white matter of the brain. White matter spongiosis is prominent in the cerebral hemispheres and brainstem fiber tracts in Kearns-Sayre syndrome.[16] Gray matter loss is also seen in the brainstem and Purkinje cell layer. Calcium deposits accumulate in the globus pallidus and thalamus.
  • Histologic studies of the heart show abnormalities of the conduction system. Large mitochondria with abnormal structure develop in both skeletal and heart muscles.
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Contributor Information and Disclosures
Author

Anna Purna Basu, PhD  BMBCh, MRCPCH, Academic Clinical Lecturer; Specialist Registrar, Pediatric Neurology, Great North Childrens Hospital, Newcastle upon Tyne

Anna Purna Basu, PhD is a member of the following medical societies: Academic Paediatrics Association (UK), British Association of Childhood Disability, British Medical Association, British Neuroscience Association, British Paediatric Neurology Association, and Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Coauthor(s)

Ewa Posner, MD, MRCP  Consultant Pediatrician, Department of Pediatrics, University Hospital of North Durham, UK

Ewa Posner, MD, MRCP is a member of the following medical societies: European Paediatric Neurology Society and Royal College of Paediatrics and Child Health

Disclosure: Nothing to disclose.

Robert McFarland, MA, MBBS, PhD, MRCP  Department of Health/HEFCE Clinical Senior Lecturer and Consultant Paediatric Neurologist, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust

Disclosure: Nothing to disclose.

D M Turnbull, MBBS, PhD, MD  Professor, Department of Neurology, University of Newcastle Upon Tyne, UK; Honorary Consultant Neurologist, Royal Victoria Infirmary, Newcastle Upon Tyne, UK

D M Turnbull, MBBS, PhD, MD is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Erawati V Bawle, MD, FAAP, FACMG  Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

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.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Anderson S, Bankier AT, Barrell BG, et al. Sequence and organization of the human mitochondrial genome. Nature. Apr 1981;290(5806):457-65. [Medline].

  2. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for humanmitochondrial DNA. Nat Genet. Oct 1999;23(2):147. [Medline].

  3. Schwartz M, Vissing J. Paternal inheritance of mitochondrial DNA. N Engl J Med. Aug 2002;347(8):576-80. [Medline].

  4. OMIM. Kearns-Sayre syndrome. Online Mendelian Inheritance in Man Web site. Available at http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?530000. Accessed April 7, 2009.

  5. Chinnery PF, DiMauro S, Shanske S, et al. Risk of developing a mitochondrial DNA deletion disorder. Lancet. Aug 14-20 2004;364(9434):592-6. [Medline].

  6. Lopez-Gallardo E, Lopez-Perez MJ, Montoya J, Ruiz-Pesini E. CPEO and KSS differ in the percentage and location of the mtDNA deletion. Mitochondrion. Sep 2009;9(5):314-7. [Medline].

  7. Remes AM, Majamaa-Voltti K, Karppa M, et al. Prevalence of large-scale mitochondrial DNA deletions in an adult Finnish population. Neurology. Mar/2005;64(6):976-81. [Medline].

  8. Schaefer AM, McFarland R, Blakely EL, et al. Prevalence of mitochondrial DNA disease in adults. Ann Neurol. Jan 2008;63(1):35-9. [Medline].

  9. Bosbach S, Kornblum C, Schroder R, Wagner M. Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain. May 2003;126(Pt 5):1231-40. [Medline]. [Full Text].

  10. Jackson MJ, Schaefer JA, Johnson MA, Morris AA, Turnbull DM, Bindoff LA. Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients. Brain. Apr 1995;118 (Pt 2):339-57. [Medline].

  11. Moraes CT, DiMauro S, Zeviani M, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. May 18 1989;320(20):1293-9. [Medline].

  12. Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf). Jul 1992;37(1):97-103. [Medline].

  13. Saneto RP, Friedman SD, Shaw DW. Neuroimaging of mitochondrial disease. Mitochondrion. Dec 2008;8(5-6):396-413. [Medline].

  14. Chu BC, Terae S, Takahashi C, et al. MRI of the brain in the Kearns-Sayre syndrome: report of four cases and a review. Neuroradiology. Oct 1999;41(10):759-64. [Medline].

  15. Anan R, Nakagawa M, Miyata M, et al. Cardiac involvement in mitochondrial diseases. A study on 17 patients with documented mitochondrial DNA defects. Circulation. Feb 15 1995;91(4):955-61. [Medline]. [Full Text].

  16. Filosto M, Tomelleri G, Tonin P, et al. Neuropathology of mitochondrial diseases. Biosci Rep. Jun 2007;27(1-3):23-30. [Medline].

  17. Andrews RM, Griffiths PG, Chinnery PF, Turnbull DM. Evaluation of bupivacaine-induced muscle regeneration in the treatment of ptosis in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Eye. Dec 1999;13 ( Pt 6):769-72. [Medline].

  18. Kornblum C, Broicher R, Walther E, et al. Cricopharyngeal achalasia is a common cause of dysphagia in patients with mtDNA deletions. Neurology. May 2001;56(10):1409-12. [Medline].

  19. Pijl S, Westerberg BD. Cochlear implantation results in patients with Kearns-Sayre syndrome. Ear Hear. Jun 2008;29(3):472-5. [Medline].

  20. Pineda M, Ormazabal A, Lopez-Gallardo E, et al. Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion. Ann Neurol. Feb 2006;59(2):394-8. [Medline].

  21. Chinnery PF, Turnbull DM. Mitochondrial DNA mutations in the pathogenesis of human disease. Mol Med Today. Nov 2000;6(11):425-32. [Medline].

  22. S DiMauro, M Hirano. Mitochondrial DNA Deletion Syndromes. GeneReviews. Available at http://www.ncbi.nlm.nih.gov/books/NBK1203/. Accessed 1/4/09.

  23. Finsterer J, Haberler C, Schmiedel J. Deterioration of Kearns-Sayre syndrome following articaine administration for local anesthesia. Clin Neuropharmacol. May-Jun 2005;28(3):148-9. [Medline].

  24. Finsterer J. Central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand. Oct 2006;114(4):217-38. [Medline].

  25. Aure K, Ogier de Baulny H, Laforet P, Jardel C, Eymard B, Lombes A. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression?. Brain. Jun 2007;130(Pt 6):1516-24. [Medline].

  26. [Guideline] Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol. May 27 2008;51(21):e1-62. [Medline].

 
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Skeletal muscle stained for both cytochrome oxidase (COX) and succinic dehydrogenase (SDH), two mitochondrial respiratory chain enzymes. Fibers that stain only for SDH and are COX-negative appear blue. Original magnification X 50.
Bilateral ptosis and external ophthalmoplegia. Top: patient looking straight ahead. Below: patient is being asked to look in the direction of the arrow in each case. Restriction of eye movements in each direction is demonstrated.
Modified Gomori Trichrome stain showing ragged red fibres. These show red staining round the periphery as well as within the sarcoplasm, giving a speckled appearance. Of the two affected muscle fibres pictured here, the one on the right shows a more extreme degree of mitochondrial proliferation and also some degeneration/vacuolation than the one on the left.
 
 
 
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