Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1987 Nov;129(2):313–326.

A morphometric study of Reye's syndrome. Correlation of reduced mitochondrial numbers and increased mitochondrial size with clinical manifestations.

C C Daugherty 1, P S Gartside 1, J E Heubi 1, K Saalfeld 1, J Snyder 1
PMCID: PMC1899719  PMID: 2823614

Abstract

Morphometric analysis of liver ultrastructure in 14 children with Reye's syndrome (RS) of varying morphologic severity was compared with that of 6 children with normal livers. Results showed reduced numbers of enlarged mitochondria in RS. Multivariant analysis identified correlations between increased mitochondrial size, decreased mitochondrial number, and severity of neurologic disease (stage). A disproportionate increase in mitochondrial area and perimeter in the RS cases with the most depressed mitochondrial number distinguished the 4 children with residual neurologic damage or death. Serum salicylate concentrations were negatively correlated with severity of morphologic alteration. Two cases of non-RS salicylate toxicity showed normal or near-normal mitochondrial size and number. In fatty liver from an autopsy specimen from a child, a child with carnitine deficiency, and a child on therapy for dermatomyositis, mitochondrial numbers were also normal. Decreased mitochondrial numbers are characteristic of RS and imply a pathophysiologic mechanism, possibly related to impaired mitochondrial replication. Synergism with other forms of mitochondrial injury, such as salicylates, hypoglycemia, or shock may influence clinical severity, progression, and outcome.

Full text

PDF
322

Images in this article

316Figure 1
on p.316
322Figure 5
on p.322
323Figure 6
on p.323

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bonnell H. J., Beckwith J. B. Fatty liver in sudden childhood death. Implications for Reye's syndrome? Am J Dis Child. 1986 Jan;140(1):30–33. doi: 10.1001/archpedi.1986.02140150032027. [DOI] [PubMed] [Google Scholar]
  2. Bove K. E., McAdams A. J., Partin J. C., Partin J. S., Hug G., Schubert W. K. The hepatic lesion in Reye's syndrome. Gastroenterology. 1975 Sep;69(3):685–697. [PubMed] [Google Scholar]
  3. Chang C. H., Uchwat F., Masalskis F., Arcinue E. L. Morphologic grading of hepatic mitochondrial alteration in Reye's syndrome: potential prognostic implication. Pediatr Pathol. 1985;4(3-4):265–275. doi: 10.3109/15513818509026900. [DOI] [PubMed] [Google Scholar]
  4. De Vivo D. C. Reye syndrome: a metabolic response to an acute mitochondrial insult? Neurology. 1978 Feb;28(2):105–108. doi: 10.1212/wnl.28.2.105. [DOI] [PubMed] [Google Scholar]
  5. Deshmukh D. R. Animal models of Reye's syndrome. Rev Infect Dis. 1985 Jan-Feb;7(1):31–40. doi: 10.1093/clinids/7.1.31. [DOI] [PubMed] [Google Scholar]
  6. Lichtenstein P. K., Heubi J. E., Daugherty C. C., Farrell M. K., Sokol R. J., Rothbaum R. J., Suchy F. J., Balistreri W. F. Grade I Reye's syndrome. A frequent cause of vomiting and liver dysfunction after varicella and upper-respiratory-tract infection. N Engl J Med. 1983 Jul 21;309(3):133–139. doi: 10.1056/NEJM198307213090302. [DOI] [PubMed] [Google Scholar]
  7. Loud A. V. A quantitative stereological description of the ultrastructure of normal rat liver parenchymal cells. J Cell Biol. 1968 Apr;37(1):27–46. doi: 10.1083/jcb.37.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ma M. H., Biempica L. The normal human liver cell. Cytochemical and ultrastructural studies. Am J Pathol. 1971 Mar;62(3):353–390. [PMC free article] [PubMed] [Google Scholar]
  9. Mitchell R. A., Partin J. C., Partin J. S., Ram M. L. Hepatic and encephalopathic components of Reye's syndrome: factor analysis of admission data from 209 patients. Neurology. 1985 Aug;35(8):1236–1239. doi: 10.1212/wnl.35.8.1236. [DOI] [PubMed] [Google Scholar]
  10. Mitchell R. A., Ram M. L., Arcinue E. L., Chang C. H. Comparison of cytosolic and mitochondrial hepatic enzyme alterations in Reye's syndrome. Pediatr Res. 1980 Nov;14(11):1216–1221. doi: 10.1203/00006450-198011000-00013. [DOI] [PubMed] [Google Scholar]
  11. Mock D. M., Scott M., Mock N. I., Thaler M. M. The proportion of mitochondrial isoenzyme of aspartate aminotransferase is not elevated in Reye's syndrome. Pediatr Res. 1983 Nov;17(11):884–888. doi: 10.1203/00006450-198311000-00009. [DOI] [PubMed] [Google Scholar]
  12. Parikh V. S., Morgan M. M., Scott R., Clements L. S., Butow R. A. The mitochondrial genotype can influence nuclear gene expression in yeast. Science. 1987 Jan 30;235(4788):576–580. doi: 10.1126/science.3027892. [DOI] [PubMed] [Google Scholar]
  13. Partin J. C., Schubert W. K., Partin J. S. Mitochondrial ultrastructure in Reye's syndrome (encephalopathy and fatty degeneration of the viscera). N Engl J Med. 1971 Dec 9;285(24):1339–1343. doi: 10.1056/NEJM197112092852402. [DOI] [PubMed] [Google Scholar]
  14. Partin J. S., Daugherty C. C., McAdams A. J., Partin J. C., Schubert W. K. A comparison of liver ultrastructure in salicylate intoxication and Reye's syndrome. Hepatology. 1984 Jul-Aug;4(4):687–690. doi: 10.1002/hep.1840040421. [DOI] [PubMed] [Google Scholar]
  15. Partin J. S., McAdams A. J., Partin J. C., Schubert W. K., McLaurin R. L. Brain ultrastructure in Reye's disease. II. Acute injury and recovery processes in three children. J Neuropathol Exp Neurol. 1978 Nov-Dec;37(6):796–819. [PubMed] [Google Scholar]
  16. Pitha J. V. Computer-assisted planimetry. Hum Pathol. 1985 Dec;16(12):1284–1285. doi: 10.1016/s0046-8177(85)80047-2. [DOI] [PubMed] [Google Scholar]
  17. REYE R. D., MORGAN G., BARAL J. ENCEPHALOPATHY AND FATTY DEGENERATION OF THE VISCERA. A DISEASE ENTITY IN CHILDHOOD. Lancet. 1963 Oct 12;2(7311):749–752. doi: 10.1016/s0140-6736(63)90554-3. [DOI] [PubMed] [Google Scholar]
  18. Robinson B. H., Taylor J., Cutz E., Gall D. G. Reye's syndrome: preservation of mitochondrial enzymes in brain and muscle compared with liver. Pediatr Res. 1978 Nov;12(11):1045–1047. doi: 10.1203/00006450-197811000-00003. [DOI] [PubMed] [Google Scholar]
  19. Schubert W. K., Partin J. C., Partin J. S. Encephalopathy and fatty liver (Reye's syndrome). Prog Liver Dis. 1972;4:489–510. [PubMed] [Google Scholar]
  20. Svoboda D. J., Reddy J. K. Pathology of the liver in Reye's syndrome. Lab Invest. 1975 May;32(5):571–579. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES