Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T08:33:24.141Z Has data issue: false hasContentIssue false
  • English
  • Français

Mitochondrial Myopathy of Cerebro-Hepato-Renal (Zellweger) Syndrome

Published online by Cambridge University Press:  18 September 2015

Harvey B. Sarnat ,
Geoffrey Machin ,
Husam Z. Darwish  and
Steven Z. Rubin
Harvey B. Sarnat*
Affiliation:
Departments of Pathology, Paediatrics, Clinical Neurosciences, and Surgery, University of Calgary Faculty of Medicine, Calgary, Alberta
Geoffrey Machin
Affiliation:
Departments of Pathology, Paediatrics, Clinical Neurosciences, and Surgery, University of Calgary Faculty of Medicine, Calgary, Alberta
Husam Z. Darwish
Affiliation:
Departments of Pathology, Paediatrics, Clinical Neurosciences, and Surgery, University of Calgary Faculty of Medicine, Calgary, Alberta
Steven Z. Rubin
Affiliation:
Departments of Pathology, Paediatrics, Clinical Neurosciences, and Surgery, University of Calgary Faculty of Medicine, Calgary, Alberta
*
Alberta Children’s Hospital, 1820 Richmond Road S.W., Calgary, Alberta, Canada T2T 5C7.
Rights & Permissions [Opens in a new window]

Summary:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The muscles of four infants with cerebro-hepato-renal (Zellweger) syndrome were studied during life and/or at necropsy. A mitochondrial myopathy was demonstrated, similar to mitochondrial alterations demonstrated in liver and brain in this disease. Muscle fibers with red-staining subsarcolemmal aggregates were identified with Gomori trichome stain in two cases. Subsarcolemmal and intermyofibrillar zones of increased concentrations of NADH-TR, SDH, and cytochrome-c-oxidase activity were demonstrated histochemically in all four cases. Degenerative and cytoarchitectural changes in muscle fibers were not found. Ultrastructural studies showed large aggregates of mitochondria and increased lipid in the subsarcolemmal and intermyofibrillar spaces. Degenerative changes in mitochondria and lipid also were demonstrated, but paracrystalline inclusions were not seen. The distribution of these changes was not uniform between patients or between different muscles in the same patient. The diaphragm was affected more severely than proximal or distal muscles of the extremities. Direct involvement of muscle mitochondria in this disease may interfere with energy metabolism and contribute to the clinical findings of hypotonia, weakness, and respiratory insufficiency. The muscle biopsy with histochemistry and electron microscopy may be used as a diagnostic adjunct in suspected cases, but the variation encountered dictates caution in the interpretation of negative findings.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 10 , Issue 3 , August 1983 , pp. 170 - 177
Copyright
Copyright © Canadian Neurological Sciences Federation 1983

References

Agamanolis, D.P., Robinson, H.B. Jr., Timmons, G.D. (1976). Cerebro-hepato-renal syndrome. Report of a case with histochemical and ultrastructural observations. J Neuropathol Exp Neurol, 35:226–246.CrossRefGoogle ScholarPubMed
Behrenberg, R.A., Pellock, J.M., DiMauro, S., et al., (1977). Lumping or splitting? ‘Opthalmoplegia-plus’ or Kearns-Sayres syndrome. Ann Neurol, 1: 37–54.Google Scholar
Bonilla, E., Schotland, D.L., DiMauro, S., Aldover, B. (1975). Electron cytochemistry of crystalline inclusions in human skeletal muscle mitochondria. J Ultrastruct Res, 51: 404–408.CrossRefGoogle ScholarPubMed
Bowen, P., Lee, C.S.N., Zellweger, H., Lindenberg, R. (1964). A familial syndrome of multiple congenital defects. Bull Johns Hopkins, 114:402–414.Google ScholarPubMed
Crosby, T.W., Chou, S.A. (1974). ‘Ragged-red’ fibers in Leigh’s disease. Neurology, 24: 49–54.Google ScholarPubMed
Danks, M.D., Tippett, P., Adams, C., Campbell, P. (1975). Cerebro-hepato-renal syndrome of Zellweger. J Pediatr, 86: 382–387.CrossRefGoogle ScholarPubMed
Della Giustina, E., Goffinet, A.M., Landrieu, P., Lyon, G. (1981). A Golgi study of the brain malformates in Zellweger’s cerebro-hepato-renal disease. Acta Neuropathol, 55: 23–28.CrossRefGoogle ScholarPubMed
DiMauro, S. (1980). Metabolic myopathies. In: Vinken, P.J., Bruyn, G.W., Ringel, S.P., eds., Handbook of Clinical Neurology, V41. North-Holland Publ. Co., Amsterdam, N.Y., Oxford, pp. 175–234.Google Scholar
DiMauro, S., Mendell, J.R., Sahenk, Z., et al. (1980). Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. Neurology, 30: 795–804.CrossRefGoogle ScholarPubMed
French, J.H., Sherard, E.S., Lubell, H., Brotz, M., Moore, C.L. (1972). Trichopoliodystrophy. I. Report of a case and biochemical studies. Arch Neurol, 26: 229–244.CrossRefGoogle ScholarPubMed
Ghatak, N.R., Hirano, A., Poon, T.P., French, J.H. (1972). Trichopoliodystrophy. II. Pathological changes in skeletal muscle and nervous system. Arch Neurol, 26: 60–72.CrossRefGoogle ScholarPubMed
Goldfischer, S., Moore, C.L., Johnson, A.B., et al. (1973). Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science, 182: 62–64.CrossRefGoogle ScholarPubMed
Jan, J.E., Hardwick, D.F., Lowry, R.B., McCormick, A.O. (1970). Cerebro-hepato-renal syndrome of Zellweger. Amer J Dis Child, 119:274–277.Google ScholarPubMed
Land, J.M., Morgan-Hughes, J.A., Clark, J.B. (1981). Mitochondrial myopathy. Biochemical studies revealing a deficiency of NADH-cytochrome-b reductase activity. J Neurol Sci, 50: 1–13.Google ScholarPubMed
Lott, I.T., Mathis, R.K., Carter, E.A., Watkins, J.B. (1979). Mitochondrial abnormalities in the cerebrohepatorenal syndrome. Ann Neurol, 6: 173–174 (abstract).Google Scholar
Luft, R., Ikkos, D., Palmieri, G., Ernster, L., Afzelius, B. (1962). A case of severe hypermetabolism of non-thyroid origin with a defect in the maintenance of mitochondrial respiratory control: A correlated clinical, biochemical, and morphologic study. J Clin Invest, 41: 1776–1804.CrossRefGoogle Scholar
Mathis, R.K., Watkins, J.B., Szczepanik-vanLeeuween, P., Lott, I.T. (1980). Liver in the cerebro-hepato-renal syndrome: Defective bile acid synthesis and abnormal mitochondria. Gastroenterology, 79: 1311–1317.CrossRefGoogle ScholarPubMed
Morgan-Hughes, J.A., Dakveniza, P., Kahn, S.N., Landon, D.N., Sherratt, R.M., Land, J.M., Clark, J.B. (1977). A mitochondrial myopathy characterized by a deficiency in reducible cytochrome b. Brain, 100: 617–640.CrossRefGoogle ScholarPubMed
Nemni, R., Mitsumoto, H., Bradley, W.G. (1981). Morphological and biochemical analysis in chronic progressive external opthalmoplegia. J Neuropathol Exp Neurol, 40: 350 (abstract).CrossRefGoogle Scholar
Odusote, K., Karpati, G., Carpenter, S. (1981). An experimental morphometric study of neutral lipid accumulation in skeletal muscles. Muscle and Nerve, 4: 3–9.CrossRefGoogle ScholarPubMed
Olson, W., Engel, W.K., Walsh, G.O., Einaugler, R. (1972). Oculocraniosomatic neuromuscular disease with ‘ragged red’ fibers. Histochemical and ultrastructural changes in limb muscles of a group of patients with idiopathic progressive external opthalmoplegia. Arch Neurol, 26: 193–211.Google Scholar
Passarge, E., McAdams, A.J. (1967). Cerebro-hepato-renal syndrome. J Pediatr, 71:691–702.CrossRefGoogle ScholarPubMed
Patton, R.G., Christie, D.L., Smith, D.W., Beckwitt, J.B. (1972). Cerebro-hepato-renal syndrome of Zellweger. Amer J Dis Child, 124: 840–844.CrossRefGoogle ScholarPubMed
Pfeifer, V., Sandhage, K. (1979). Licht-und elektronenmikroskopische Leberbefunde beim Cerebro-Hepato-Renalen Syndrome nach Zellweger (Peroxisomen-Defizienz). Virch Arch A path Anat Histol, 384: 269–284.CrossRefGoogle Scholar
Stadhouders, A.M. (1981). Mitochondrial ultrastructural changes in muscular diseases. In: Mitochondria and Muscular Diseases, Busch, H.F.M., Jennekens, F.G.I., Scholte, H.R., eds. Mefarb. v., Beetsterzwaag, The Netherlands, pp 113–132.Google Scholar
Tassin, S., Walter, G.F., Brucher, J.M., Rousseau, J.J. (1980). Histochemical and ultrastructural analysis of the mitochondrial changes in a familial mitochondrial myopathy. Neuropathol Appl Neurobiol, 6: 337–347.Google Scholar
Trijbels, J.M.F., Monnens, L.A.H., Bakkeren, J.A.J.M., Willems, J.L., Sengers, R.C.A. (1981). Mitochondrial abnormalities in the cerebro-hepato-renal syndrome of Zellweger. In: Mitochondria and Muscular Disease, Busch, H.F.M., Jennekens, F.G.I., Scholtz, H.R., eds., Mefarb.v., Beetsterzwaag, The Netherlands, pp 187–190.Google Scholar
Volpe, J.J., Adams, R.D. (1972). Cerebro-hepato-renal syndrome of Zellweger: An inherited disorder of neuronal migration. Acta Neuropathol, 20: 175–198.Google ScholarPubMed
Walter, G.F., Tassin, S., Brucher, J.M. (1981). Familial mitochondrial myopathies. Acta Neuropathol Suppl VII: 283–286.Google Scholar
Willems, J.L., Monnens, L.A.H., Trijbels, J.M.F., et al. (1977). Leigh’s encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics, 60: 850–857.CrossRefGoogle Scholar