Renal Fanconi syndrome: first sign of partial respiratory chain complex IVdeficiency

A 2-year-old boy who developed hypophosphatemic rickets without signs of mu scular weakness or neurological disturbances is presented. Biochemical find ings included hypophosphatemia, metabolic acidosis, hypouricemia, hyperphos phaturia, severe glucosuria, generalized hyperaminoaciduria, hypercalciuria , proteinuria with elevated excretion of IgG, transferrin, albumin and high levels of cr-l-microglobulin, Urine concentration capacity and creatinine clearance were normal. Lactaturia without elevated levels of plasma lactate and a high urinary excretion of P-hydroxybutyrate were suggestive for mito chondriopathy. Partial deficiency of cytochrome c oxidase (complex IV of th e respiratory chain) was found in skeletal muscle. A renal biopsy specimen demonstrated enlarged mitochondria with abnormal arborization and disorient ation of the cristae in the proximal tubular cells. Reduced activity of mit ochondrial cytochrome c oxidase in tubular cells could be demonstrated by u ltracytochemistry. In conclusion, rickets due to the renal Fanconi syndrome can be the first clinical sign of mitochondrial cytopathies without extrar enal symptoms. Elevated excretion of lactate and ketone bodies in urine may serve as a diagnostic marker.