Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.

The Investigator will evaluate the safety and efficacy of a 4-weeks treatment with sodium phenylbutyrate in patients with pyruvate dehydrogenase complex deficiency. Efficacy will be evaluated based on biochemical endpoints (blood lactate and pyruvate).

Inclusion criteria

• Subject must be older than 3 months old and younger than 18 years old.
• Clinical diagnosis of PDC deficiency confirmed by DNA testing showing a missense mutation in the PDHA1 gene.
• Lactate concentration ≥ 2.5 mmol/l or ≥ 2 mmol/l, respectively in venous or arterial blood samples.
• Provision of signed and dated informed consent form by the parents/legal guardians of the patient
• Negative pregnancy test for women of childbearing potential, and agree to use effective form of contraception until 6 weeks post treatment.

Exclusion criteria

• Frameshift or nonsense mutations of the PDHA1 gene.
• Defects affecting any gene encoding PDC subunits other than PDHA1
• Secondary forms of lactic acidosis (e.g. impaired oxygenation or circulation).
• Tracheostomy or requirement for artificial ventilation.
• Hyperlactatemia or organic acidosis associated with other metabolic disorders (e.g. biotinidase deficiency, primary disorders of gluconeogenesis, organic acidurias, primary defects of fatty acids oxidation)
• Evidence of hepatic insufficiency, renal insufficiency, edema with sodium retention, cardiac arrhythmia, congenital heart defects, hypertension, blood dyscrasia, symptomatic pancreatitis, or inflammatory bowel disease.
• Any clinical condition or medications known to significantly affect renal clearance.
• Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study.
• Known allergic reactions to components of the study agent.
• Treatment with another investigational drug or other intervention (including DCA) or participation in a clinical study with an investigational drug within 6 months prior to enrolment.
• Pregnancy or lactation.