Reversion of hypertrophic cardiomyopathy in a patient with de¢ciency of the mitochondrial copper binding protein Sco2: Is there a potential effect of copper? P. FREISINGER 1 , R. HORVATH 2 , C. MACMILLAN 3 , J. PETERS 1 and M. JAKSCH 2 * 1 Metabolic Disease Center, Munich-Schwabing, Children’s Hospital and Institute of Medical Genetics, Technical University, Munich; 2 Metabolic Disease Center, Munich-Schwabing and Institute of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Munich, Germany; 3 Department of Neuropediatrics, Children’s Hospital, University of Illinois, Chicago, Illinois, USA *Correspondence: Metabolic Disease Center Munich-Schwabing, Koelner Platz 1, 80804 Mˇnchen, Germany. E-mail: michaela.jaksch@lrz.uni-muenchen.de MS received 22.07.03 Accepted 31.10.03 Summary: MutationsinSco2,aproteininvolvedincoppertraffickingtotheter- minal enzyme of the respiratory chain, cytochrome c oxidase, results in infantile hypertrophic cardioencephalomyopathy. We have recently shown that copper-histidine (Cu-his) supplementation of Sco2-deficient myoblasts rescues COX activity in vitro.Here,wereportapatientwith SCO2 mutations and with resolution of severe hypertrophic cardiomyopathy. Weighing up the evidence, the most likely explanation for the improved cardiac function in this patient was the subcutaneous application of Cu-his. Isolated deficiency of cytochrome c oxidase (COX or complex IV), the terminal enzymeoftherespiratorychain(RC)resultsinawideclinicalspectrumrangingfrom late childhood-onset myopathies to severe neonatal-onset multisystem disorders affectingmainlymuscle,heartandCNS(forreviewseeShoubridge2001).Inarecent report, the incidence of all mitochondrial encephalopathies in preschool children in Sweden was estimated as 1 in 11000 (Darin et al 2001). In our collective, reflecting the southern part of Germany, the frequency of isolated COX deficiency alone is estimated at about 1 in 20000 (unpublished data). COX catalyses the reduction of molecular oxygen by reduced cytochrome c. The complex is embedded in the inner mitochondrial (mt) membrane and is composed of 13 subunits. Three subunits (COX I^III) are encoded by the mitochondrial DNA and form the catalytic core of the enzyme. Ten subunits, encoded by nuclear DNA, are thought to modify or to stabilize the complex. For its enzymatic J.Inherit.Metab.Dis. 27(2004)67^79 # SSIEMandKluwerAcademicPublishers.PrintedintheNetherlands 67