Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
Use of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
In this study phenylbutyrate is used for patients with pyruvate dehydrogenase complex
 deficiency. The aim of the study is to investigate the safety and efficacy of therapy.
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:

 1. Subject must be older than 3 months old and younger than 18 years old.

 2. Clinical diagnosis of PDC deficiency confirmed by DNA testing showing a missense
 mutation in the PDHA1 gene.

 3. Lactate concentration ≥ 2.5 mmol/l or ≥ 2 mmol/l, respectively in venous or arterial
 blood samples.

 4. Provision of signed and dated informed consent form by the parents/legal guardians of
 the patient

 5. Negative pregnancy test for women of childbearing potential, and agree to use
 effective form of contraception until 6 weeks post treatment.

 Exclusion Criteria:

 1. Frameshift or nonsense mutations of the PDHA1 gene.

 2. Defects affecting any gene encoding PDC subunits other than PDHA1

 3. Secondary forms of lactic acidosis (e.g. impaired oxygenation or circulation).

 4. Tracheostomy or requirement for artificial ventilation.

 5. 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)

 6. Evidence of hepatic insufficiency, renal insufficiency, edema with sodium retention,
 cardiac arrhythmia, congenital heart defects, hypertension, blood dyscrasia,
 symptomatic pancreatitis, or inflammatory bowel disease.

 7. Any clinical condition or medications known to significantly affect renal clearance.

 8. 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.

 9. Known allergic reactions to components of the study agent.

 10. 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.

 11. Pregnancy or lactation.