title: Long-term safety of dichloroacetate in congenital lactic acidosis.
abstract: We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1α subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 h) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Abdelmalak
authors.forename: Alicia
authors.initials: A
authors.lastname: Lew
authors.forename: Ryan
authors.initials: R
authors.lastname: Ramezani
authors.forename: Albert L
authors.initials: AL
authors.lastname: Shroads
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Coats
authors.forename: Taimour
authors.initials: T
authors.lastname: Langaee
authors.forename: Meena N
authors.initials: MN
authors.lastname: Shankar
authors.forename: Richard E
authors.initials: RE
authors.lastname: Neiberger
authors.forename: S H
authors.initials: SH
authors.lastname: Subramony
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000151:congenital / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003999:Dichloroacetic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D003999:Dichloroacetic Acid