Journal
MOLECULAR GENETICS AND METABOLISM
Volume 109, Issue 2, Pages 139-143Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2013.03.019
Keywords
Congenital lactic acidosis; Dichloroacetate; Pyruvate dehydrogenase; Respiratory chain; Clinical trial
Funding
- University of Florida Clinical and Translational Science Institute
- NIH/NCATS Clinical and Translational Science Award [UL1 TR000064]
Ask authors/readers for more resources
We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the El et subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (I 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. (C) 2013 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available