Abstract
A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol/l; n<2), pyruvate (0.4 mmol/l; n<0.05) and alanine levels were found in serum with an abnormal lactate/pyruvate ratio (>30; n<15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated “ragged red fibres” were found by light microscopy; muscle fibres were found to contain subsarcolemmal aggregates of mitochondria, lipid droplets and glycogen by electromicroscopical methods. More-over, mitochondria with a typical circular arrangement of cristae were noticed.
In liver homogenates normal activities of pyruvate carboxylase and pyruvate dehydrogenase complex were found; in liver mitochondria also succinate-cytochrome-c-oxidoreductase activity was normal. However, in muscle no succinate-cytochrome-c-oxidoreductase activity was detectable.
The patient became increasingly lethargic and died because of sepsis at 5 months of age.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465
Atkin BM, Buist NR, 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
Barth PG, Scholte HR, Berden JA, van der Klei-van Moorsel JM, Luyt-Houwen IEM, van T Veer-Korthof ETH, van der Harten JJ, Sobotka-Plojhar MA (1983) An X-linked mitochondrial disease afferting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol Sci 62: 327–355
van Biervliet JPGM, Bruinvis L, Ketting D, de Bree PK, van der Heiden C, Wadman SK, Willems JL, Bookelman H, van Haelst U, Monnens LAH (1977) Hereditary mitochondrial myopathy with lactic acidemia, a DeToni-Fanconi-Debré syndrome, and a defective respiratory chain in voluntary striated muscles. Pediatr Res 11:1088–1093
Egger J, Wilson J (1983) Mitochondrial inheritance in a mitochondrially mediated disease. N Engl J Med 309:142–146
Egger J, Wynne-Williams CJE, Erdohazi M (1982) Mitochondrial cytopathy or Leigh's syndrome? Mitochondrial abnormalities in spongiform encephalopathies. Neuropediatrics 13:219–224
van Gelder BF, Slater EC (1962) The extinction coefficient of cytochrome c. Biochim Biophys Acta 58:593–595
Heiman-Patterson TD, Bonilla E, DiMauro S, Foreman J, Schotland DL (1982) Cytochrome-c-oxidase deficiency in a floppy infant. Neurology 32:898–901
DiMauro S, Mendell JR, Sahenk Z, Bachman D, Scarpa A, Scofield RM, Reiner C (1980) Fetal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. Neurology 30:795–804
Miyabayashi S, Narisawa K, Tada K, Sakai K, Kobayashi K, Kobayashi Y (1983) Two siblings with cytochrome c oxidase deficiency. J Inherited Metab Dis 6:121–122
Sengers RCA, Fischer JC, Trijbels JMF, Ruitenbeek W, Stadhouders AM, ter Laak HJ, Jaspar HHJ (1983) A mitochondrial myopathy with a defective respiratory chain and carnitine deficiency. Eur J Pediatr 140:332–337
Schofield PJ, Griffiths LR, Rogers SH, Wise G (1980) An improved method for the assay of platelet pyruvate dehydrogenase. Clin Chim Acta 108:219–227
Scholte HR, Busch HFN, Barth PG, Beekman RP, Berden JA, Duran M, Luyt-Houwen IEM, Przyrembel H, Roth B, de Vries S (1983) Carnitine deficiency and mitochondrial respiratory chain blockade. In: Scarlato G, Cerri C (eds) Mitochondrial pathology in muscle diseases. Piccin Medical Books, Padua, pp 215–228
Willems JL, Monnens LAH, Trijbels JMF, Veerkamp JH, Meyer AEFH, van Dam K, van Haelst U (1977) Leigh's encephalomyelopathy in a patient wity cytochrome c oxidase deficiency in muscle tissue. Pediatrics 60:850–857
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Behbehani, A.W., Goebel, H., Osse, G. et al. Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase. Eur J Pediatr 143, 67–71 (1984). https://doi.org/10.1007/BF00442753
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00442753