Fatal infantile myopathy

Defects of complex IV. These disorders, also termed COX deficiency, have clinical phenotypes that fall into two main groups one in which myopathy is the predominant or exclusive manifestation and another in which brain dysfunction predominates (Fig. 42-3). In the first group, the most common disorder is fatal infantile myopathy, causing generalized weakness, respiratory insufficiency and death before age 1 year. There is lactic acidosis and renal dysfunction, with glycosuria, phosphaturia and aminoaciduria, also termed DeToni-Fanconi-Debre syndrome. The association of myopathy and cardiopathy in the same patient and myopathy and liver disease in the same family has also been described [14]. 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

NING, C., KUHARA, T INOUE, Y, ZHANG, C.H., MATSUMOTO, M., SHINKA, T., FURUMOTO, T., YOKOTA, K., MATSUMOTO, I., Gas chromatographic mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with De Toni-Fanconi-Debre syndrome, Acta Paediatrica Japonica, 1996,38,661-666. 

Ml 8. Miiller-Hocker, J., Ibel, H., Paetzke, I., Deufel, T., Endres, W., Kadenbach, B., Gokel, J. M., and Hubner, G., Fatal infantile mitochondrial myopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies. Virchows Arch. A Pathol. Anat. Histopathol. 419, 55-362 (1991). 

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