{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T17:30:25Z","timestamp":1769275825305,"version":"3.49.0"},"reference-count":34,"publisher":"BMJ","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,4,5]]},"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Homoplasmic maternally inherited, m.14674T&gt;C or m. 14674T&gt;G mt-tRNA<jats:sup>Glu<\/jats:sup> mutations have recently been identified in reversible infantile cytochrome c oxidase deficiency (or \u2018benign COX deficiency\u2019). This study sought other genetic defects that may give rise to similar presentations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Eight patients from seven families with clinicopathological features of infantile reversible cytochrome c oxidase deficiency were investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study reviewed the diagnostic features and performed molecular genetic analyses of mitochondrial DNA and nuclear encoded candidate genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients presented with subacute onset of profound hypotonia, feeding difficulties and lactic acidosis within the first months of life. Although recovery was remarkable, a mild myopathy persisted into adulthood. Histopathological findings in muscle included increased lipid and\/or glycogen content, ragged-red and COX negative fibres. Biochemical studies suggested more generalised abnormalities than pure COX deficiency. Clinical improvement was reflected by normalisation of lactic acidosis and histopathological abnormalities. The m.14674T&gt;C mt-tRNA<jats:sup>Glu<\/jats:sup> mutation was identified in four families, but none had the m. 14674T&gt;G mutation. Furthermore, in two families pathogenic mutations were also found in the nuclear <jats:italic>TRMU<\/jats:italic> gene which has not previously been associated with this phenotype. In one family, the genetic aetiology still remains unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Benign COX deficiency is better described as \u2018reversible infantile respiratory chain deficiency\u2019. It is genetically heterogeneous, and patients not carrying the m.14674T&gt;C or T&gt;G mt-tRNA<jats:sup>Glu<\/jats:sup> mutations may have mutations in the <jats:italic>TRMU<\/jats:italic> gene. Diagnosing this disorder at the molecular level is a significant advance for paediatric neurologists and intensive care paediatricians, enabling them to select children with an excellent prognosis for continuing respiratory support from those with severe mitochondrial presentation in infancy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2011.089995","type":"journal-article","created":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T04:52:32Z","timestamp":1316494352000},"page":"660-668","source":"Crossref","is-referenced-by-count":64,"title":["Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial 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