[1] The PDC is a multi-enzyme complex that plays a vital role as a key regulatory step in the central pathways of energy metabolism in the mitochondria.

The neurological form of PDCD contributes to hypotonia, poor feeding, lethargy and structural abnormalities in the brain.

[8] Male infants that reach full term display more severe symptoms than females, and exhibit high mortality within the first few years of life [9][7] Prenatal onset may present with non-specific signs such as low Apgar scores and small for gestational age.

[7] Metabolic disturbances may also be considered with poor feeding and lethargy out of proportion to a mild viral illness, and especially after bacterial infection has been ruled out.

[citation needed] The clinical presentation of congenital PDH deficiency is typically characterized by heterogenous neurological features that usually appear within the first year of life.

[3] *In less severe cases, signs of lactic acidosis can include ataxia and episodes may only occur when ill, under stress, or after consuming high amounts of carbohydrates.

[citation needed] The most commonly seen form of PDCD is caused by mutations in the X-linked E1 alpha gene, PDHA1,[11] and is approximately equally prevalent in both males and females.

[14] The LIAS gene is responsible for synthesizing lipoic acid, a cofactor required by the pyruvate dehydrogenase complex.

[16] Direct treatment that stimulates the pyruvate dehydrogenase complex (PDC), provides alternative fuels, and prevents acute worsening of the syndrome.

[19] With the ketogenic diet, ATP is synthesized by the catabolism of fatty acids rather than glucose, which produces the ketone bodies, 3-beta-hydroxybutyrate, acetoacetate, and acetone.

[18] The ketogenic diet has several long term drawbacks, including pancreatitis, sialorrhea and obstipation to vomiting.

PDHA1 was shown to be a good candidate for gene therapy using an adeno associated virus (AAV2) to express the protein in vitro nearly 15 years ago;[22] however, research was discontinued.

An AAV9 vector is currently used in an FDA-approved gene therapy of spinal muscular atrophy (SMA) in infants and children.