Congenital lactic acidosis, also known as CLA, is an inherited inborn error of metabolism (IEM) characterized by the build-up of lactic acid in the body (lactic acidosis). The incidence of congenital lactic acidosis is unknown. One estimate places the incidence at 250-300 live births per year in the United States. CLA is typically caused by a mutation in the genes encoding the pyruvate dehydrogenase complex (PDC) leading to deficiencies in the function and efficiency of pyruvate dehydrogenase complex proteins, which are located in the mitochondria. Collectively the PDC converts pyruvate, NAD+, coenzyme A into acetyl-CoA, CO2, and NADH. While CLA-associated defects have been identified in all 3 enzymes of the PDC complex, the E1-alpha subunit is the most commonly mutated form. Defects in the citric acid cycle due to PDC deficiency deprives the body of energy and leads to an abnormal build-up of lactic acid in tissues and biofluids. CLA has either an autosomal recessive or X-linked mode of inheritance. There are two forms of CLA: severe and mild. Severe cases of CLA manifest in the neonatal period while milder cases may not manifest until early adulthood. Symptoms may be persistent or brought on by an event causing stress, such as an asthma attack, seizure, or infection. Symptoms in the neonatal form of CLA include hypotonia, lethargy, vomiting, and tachypnea. As the disease progresses, it can cause developmental delays, cognitive disabilities, abnormal development of the face and head, and organ failure. Treatments for CLA that are occasionally used include the ketogenic diet and dichloroacetate.

Congenital Lactic Acidosis References

Citric Acid Cycle References