title: Renal manifestations of congenital lactic acidosis.
abstract: Congenital lactic acidoses (CLAs) constitute a group of rare inborn errors of mitochondrial metabolism in which cellular energy failure is the defining biochemical abnormality. We report the principal manifestations of renal dysfunction in 35 children with CLA caused by defects in either the pyruvate dehydrogenase multienzyme complex or one or more components of the respiratory chain. The most prominent renal abnormalities included bicarbonaturia, phosphaturia, hypercalciuria, complete Fanconi's syndrome, proteinuria, and decreased glomerular filtration rate. These data were compared with those from 79 previously published cases. Clinical manifestations of renal dysfunction in CLA are common and may be the first presenting sign of the disease. The glomerulus and proximal renal tubule appear to be the anatomic sites most vulnerable to abnormal mitochondrial energy transduction. We propose that the primary defect in mitochondrial energy metabolism, together with the consequent intracellular accumulation of lactate and hydrogen ions, precipitates a state of tissue injury that, unless interrupted, becomes self-perpetuating and ultimately leads to renal cell death.
authors.affiliation: Department of Pediatrics, Division of Nephrology, and the General Clinical Research Center, University of Florida, Gainesville, FL, USA. neibere@peds.ufl.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Neiberger
authors.forename: Jaime C
authors.initials: JC
authors.lastname: George
authors.forename: Leigh Ann
authors.initials: LA
authors.lastname: Perkins
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: Alan D
authors.initials: AD
authors.lastname: Hutson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
mesh_terms: D000140:Acidosis, Lactic / Q000150:complications* / Q000151:congenital / Q000188:drug therapy; D000293:Adolescent; D000328:Adult; D001639:Bicarbonates / Q000097:blood / Q000652:urine; D001806:Blood Urea Nitrogen; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood / Q000652:urine; D003999:Dichloroacetic Acid / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000209:etiology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000150:complications*; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood
chemical_list: D001639:Bicarbonates; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D003404:Creatinine; D002118:Calcium