Deletions in the mitochondrial DNA and decrease in the oxidative phosphorylation activity of children with fanconi syndrome secondary to antiblastic therapy

The aim of this study is to verify whether there are deletions in mitochond rial DNA (mtDNA) and disorders in oxidative phosphorylation (Ox-phos) compl exes in the pathogenesis of secondary Fanconi syndrome (FS). We studied 18 children with tumors who were previously treated with chemotherapy and were off therapy for at least 1 year. All the children had normal renal functio n at diagnosis. Only 4 children received ifosfamide (IFO) and platinum comp ounds. We evaluated renal function, Ox-phos activity measured on platelets, and mtDNA extracted from platelets for all patients. Only 2 patients, both treated with IFO and carboplatinum (CARBO) for Wilms' tumor and germ-cell tumor, respectively, developed FS 1 and 3 years after termination of therap y. They had decreased activities of Ox-phos that were statistically signifi cant only for nicotinamide adenine dinucleotide (NAD)-reduced cytochrome-c reductase and cytochrome-c oxidase and specific and unidentified deletions In mtDNA that were not maternally inherited. Our data suggest that treatmen t with IFO and CARBO might be responsible for deletions in mtDNA, decreased activity of Ox-phos, and impaired rates of transport of D-glucose, phospha te, and amino acids. (C) 1999 by the National Kidney Foundation, Inc.