X-Linked Leigh's syndrome

Human Genetics volume 62, pages52–59(1982)Cite this article

Summary

Two male half siblings developed rapid progression of neurologic symptoms at 11/2 and 21/2 years of age. Neither boy had a metabolic acidosis. Characteristic features of subacute necrotizing encephalomyelopathy, the neuropathologic basis of Leigh's syndrome, were demonstrated at autopsy. X-linkage of the disorder was considered because the boys had different fathers. An X-linked form of Leigh's syndrome was supported by a review of the literature, which showed an unexplained male/female ratio in Leigh's syndrome of 1.83/l, and a significant excess of male-male siblings. An X-linked form of Leigh's syndrome would explain the excess of males, and may account for some of the clinical and biochemical heterogeneity.

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References

  1. Atkin BM, Buist NRM, Utter MF, Leiter AB, Banker BQ (1979) Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh's disease. Pediatr Res 13:109–116

    Google Scholar 

  2. Benke PJ, Parker JC (1981) Unpublished observations

  3. Biass JP, Cederbaum SD, Dunn HE (1976) Biochemical abnormalities in Leigh's disease. Lancet 1:1237–1238

    Google Scholar 

  4. Borit A (1971) Leigh's necrotizing encephalomyelopathy. Arch Ophthalmol 85:438–442

    Google Scholar 

  5. Brahms M, Collins GH, Crosley CJ (1979) Rapidly fatal subacute necrotizing encephalomyelopathy (Leigh's syndrome) in a five-year-old boy Clin Pediatr (Phila) 18:506–508

    Google Scholar 

  6. Brandt NJ, Terenius L, Jacobsen BB, Klinken L, Nordius A, Brandt S, Blegvad K, Yssing M (1980) Hyper-endorphin syndrome in a child with necrotizing encephalomyelopathy. N Engl J Med 303:914–916

    Google Scholar 

  7. Carleton CC, Collins GH, Schimpff RD (1976) Subacute necrotizing encephalopathy (Leigh's disease): Two unusual cases. South Med J 69:1301–1305

    Google Scholar 

  8. Chi JG, Yoo HW, Chang KH, Kim CW, Moon HR, Ko KW (1981) Leigh's subacute necrotizing encephalomyelopathy: possible diagnosis by CT scan. Neuroradiology 22:141–144

    Google Scholar 

  9. Cooper JR, Pincus JH (1973) Thiamine triphosphate deficiency in Leigh's disease. In: Homes FA, van den Berg CJ (eds) Inborn errors of metabolism. Academic Press, New York, pp 122–127

    Google Scholar 

  10. Crosby TW, Chou SM (1974) “Ragged-red” fibers in Leigh's disease. Neurology 24:49–54

    Google Scholar 

  11. DeVivo DC, Haymond MW, Obert KA, Nelson JS, Pagliara AS (1979) Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh's disease). Ann Neurol 6:483–494

    Google Scholar 

  12. Dunn HG, Dolman CL (1972) Necrotizing encephalomyelopathy. Report of a case with manifestations resembling Behr's syndrome. Eur Neurol 7:34–55

    Google Scholar 

  13. Eisengart MA, Powers JM, Rose AL (1974) Subacute necrotizing encephalomyelopathy. (Rapidly fatal course of Leigh's disease in a 5-year-old child). Am J Dis Child 127:730–732

    Google Scholar 

  14. Evans OB (1981) Pyruvate decarboxylase deficiency in subacute necrotizing encephalomyelopathy. Arch Neurol 38:515–519

    Google Scholar 

  15. Evans OB, Kilroy GM (1978) Acetazolamide in the treatment of pyruvate dysmetabolism syndromes. Arch Neurol 35:302–315

    Google Scholar 

  16. Farmer TW, Veath L, Miller AL, O'Brien JS, Rosenberg RN (1973) Pyruvate decarboxylase deficiency in a patient with subacute necrotizing encephalomyelopathy. Neurology 23:429

    Google Scholar 

  17. Feigin I, Kim HS (1977) Subacute necrotizing encephalomyelopathy in a neonate infant. J Neuropathol Exp Neurol 36:364–372

    Google Scholar 

  18. Gordon N, Marsden HB, Lewis DM (1974) Subacute necrotizing encephalomyelopathy in three siblings. Dev Med Child Neurol 16:64–78

    Google Scholar 

  19. Greenwood RS, DeVivo DC, Nelson JS, Dodson WE, Raiche ME, Gado M, Haymond MW, Prensky AL (1975) An autosomal dominant form of necrotizing encephalomyelopathy resembling a spinocerebellar degeneration. Trans Am Neurol Assoc 100:47–51

    Google Scholar 

  20. Grobe H, Bassewitz DB v, Dominick HC, Pfeifer RA (1975) Subacute necrotizing encephalopathy. Acta Paediatr Scand 64:755–762

    Google Scholar 

  21. Grover WD, Auerbach VH, Patel MS (1972) Biochemical studies and therapy in subacute necrotizing encephalomyelopathy (Leigh's syndrome). J Pediatr 81:39–44

    Google Scholar 

  22. Guggenheim MA (1981) Personal communication

  23. Guggenheim MA, Stumpf DA (1977) Familial metabolic disease with clinicopathological findings of both Leigh's disease and adult-type spinocerebellar degeneration. Ann Neurol 2:264–265

    Google Scholar 

  24. Hansen TL, Christensen E, Brandt NJ (1982) Studies on pyruvate carboxylase, pyruvate decarboxylase and lipoamide dehydrogenase in subacute necrotizing encephalomyelopathy. Acta Paediatr Scand 71:263–267

    Google Scholar 

  25. Hirschman GH, Chan JCM (1978) Complex acid-base disorders in subacute necrotizing encephalomyelopathy (Leigh's syndrome). Pediatrics 61:278–281

    Google Scholar 

  26. Hommes FA (1973) Discussion. In: Hommes FA, van den Berg CJ (eds) Inborn errors of metabolism. Academic Press, New York, p 127

    Google Scholar 

  27. Hommes FA, Polman HA, Reerink JD (1968) Leigh's encephalomyelopathy: An inborn error of glucogenesis. Arch Dis Child 43:423

    Google Scholar 

  28. Horner FA, Ho Choi B (1980) A new clinical pathologic entity simulating Leigh's disease. Neurology 29:354

    Google Scholar 

  29. Jellinger K, Zimprich H, Muller D (1973) Relapsing form of subacute necrotizing encephalomyelopathy. Neuropaediatrie 4:314–321

    Google Scholar 

  30. Kalimo H, Lundberg PO, Olsson Y (1979) Familial subacute necrotizing encephalomyelopathy of the adult form (adult Leigh's syndrome). Ann Neurol 6:200–206

    Google Scholar 

  31. Kamoshita S, Aguilar MJ, Landing BH (1968) Infantile subacute necrotizing encephalomyelopathy. Am J Dis Child 116:120–129

    Google Scholar 

  32. Kissach AW, Currie S, Harriman DGF, Littleword JM, Payne RB, Walker BE (1974) Leigh's disease and failure of automatic respiration. Lancet 2:662

    Google Scholar 

  33. Kohlschutter A, Kraus-Ruppert R, Rohrer T, Herschkowitz NN (1978) Myelin studies in a case of subacute necrotizing encephalomyelopathy (SNE). J Neuropathol Exp Neurol 37:155–164

    Google Scholar 

  34. Lahl R (1981) Juvenile Form der subakuten nekrotisierenden Encephalomyelopathie (Leigh) mit ungewöhnlicher ZNS-Lokalisation. Acta Neuropathol (Berl) 55:237–242

    Google Scholar 

  35. Leigh D (1951) Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 14:216–221

    Google Scholar 

  36. Lott IA, Shannon DC (1980) Central respiratory pathology of Leigh disease. Neurology 30:354

    Google Scholar 

  37. McCandless DW, Hodgkin WE (1977) Subacute necrotizing encephalomyelopathy (Leigh's disease). Pediatrics 60:935–936

    Google Scholar 

  38. Montpetit VJA, Andermann F, Carpenter S, Fawcett JS, Zborowska-Sluis D, Giberson HR (1971) Subacute necrotizing encephalomyelopathy. A review and a study of two families. Brain 94:1–30

    Google Scholar 

  39. Moosa A (1978) Motor nerve conduction velocities in Leigh's encephalomyelopathy. Arch Dis Child 353:62–65

    Google Scholar 

  40. Murphy JV (1973) Subacute necrotizing encephalomyelopathy (Legh's disease): Detection of the heterozygous carrier state. Pediatrics 51: 710–714

    Google Scholar 

  41. Murphy JV, Isuhashi F, Weinberg MB, Utter MF (1981) Pyruvate carboxylase deficiency: an alleged biochemical cause of Leigh's disease. Pediatrics 68:401–404

    Google Scholar 

  42. Ollivier AD, Diebler C (1980) Tomodensitometric cranienne dans la maladie Leigh. Nouv Presse Med 9:2355

    Google Scholar 

  43. Pincus JH (1972) Subacute necrotizing encephalomyelopathy (Leigh's disease): A consideration of clinical features and etiology. Dev Med Child Neurol 14:87–101

    Google Scholar 

  44. Pincus JH, Cooper JR, Murphy JV, Rabe EF, Lonsdale D, Dunn HG (1973) Thiamine derivatives in subacute necrotizing encephalomyelopathy. Pediatrics 51:716–721

    Google Scholar 

  45. Plaitakis A, Whetsell WO, Cooper JR, Yahr MD (1980) Chronic Leigh disease: a genetic and biochemical study. Ann Neurol 7:304–310

    Google Scholar 

  46. Reed MA (1976) Leigh's disease: A family study. Lancet 1:1237

    Google Scholar 

  47. Robinson F, Solitare GB, Lemarche JB, Levy LL (1967) Necrotizing encephalomyelopathy of childhood. Neurology 17:472–482

    Google Scholar 

  48. Salcedo JR (1981) Personal communication

  49. Salcedo JR, Hodjati H, Hirschman GH, Chan JCM (1976) Distal renal tubular acidosis in an infant with Leigh's syndrome. Pediatr Res 10:443

    Google Scholar 

  50. Saudubray C, Marsac C, Charpentier C, Cathelineau L, Besson Leaud M, Leroux JP (1976) Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings. Acta Paediatr Scand 65:717–724

    Google Scholar 

  51. Sauer RN, Ellis WG, Dreyfus PM (1978) Evidence for two biochemically distinct diseases underlying subacute necrotizing encephalomyelopathy (Leigh disease). Neurology 28:349

    Google Scholar 

  52. Schwartz WJ, Hutchison HT, Berg BO (1981) Computerized tomography in subacute necrotizing encephalomyelopathy (Leigh disease). Ann Neurol 10:268–271

    Google Scholar 

  53. Simopoulos AP, Roth JA, Golde DW, Bartter FC (1972) Subacute necrotizing encephalomyelopathy with vacuolated cells in the bone marrow. Neurology 22:1257–1267

    Google Scholar 

  54. Tada K, Takada G, Omura K, Itokawa Y (1978) Congenital lactic acidosis due to pyruvate carboxylase inhibitor. Eur J Pediatr 127: 141–147

    Google Scholar 

  55. Tang TT, Good TA, Dyken PR, Johnson SD, McCready SR, Sy ST, Lardy HA, Rudolph FB (1972) Pathogenesis of Leigh's encephalomyelopathy. J Pediatr 81:189–190

    Google Scholar 

  56. Toshima K, Kuroda Y, Hashimoto T, Ito M, Watanabe T, Miyao M, Ii K (1982) Enzymologic studies and therapy of Leigh's disease associated with pyruvate decarboxylase deficiency. Pediatr Res 16: 430–435

    Google Scholar 

  57. Vuia O (1975) The cortical form of subacute necrotizing encephalopathy of the Leigh type. J Neurol Sci 26:295–304

    Google Scholar 

  58. Willems JL, Monnens LAH, Trijbels JMH, Veerkamp JH, Meyer AEFH, VanDam K, Van Haelst U (1977) Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics 60:850–857

    Google Scholar 

  59. Zanetti G (1978) Encefalomielopatia necrotizzante subacuta (tipo Leigh) con acidosi lattica. Pathologica 70:63–78

    Google Scholar 

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Affiliations

  1. Mailman Center and the Departments of Pediatrics and Pathology, University of Miami School of Medicine, 33101, Miami, FL, USA

    Paul J. Benke, Joseph C. Parker Jr., Marie-Louise Lubs, Judith Benkendorf & Anne E. Feuer

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  1. Paul J. Benke
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  2. Joseph C. Parker Jr.
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  3. Marie-Louise Lubs
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  4. Judith Benkendorf
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  5. Anne E. Feuer
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Correspondence to Paul J. Benke.

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Benke, P.J., Parker, J.C., Lubs, ML. et al. X-Linked Leigh's syndrome. Hum Genet 62, 52–59 (1982). https://doi.org/10.1007/BF00295603

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Keywords

  • Internal Medicine
  • Metabolic Disease
  • Characteristic Feature
  • Neurologic Symptom
  • Metabolic Acidosis