Lactic Acidosis occurs when lactate and other molecules, called protons, accumulate in bodily tissues and fluids faster than the body can remove them. Lactic acidosis can have many different causes and is often present in severely ill patients hospitalized in intensive care units. Congenital (present at birth) lactic acidosis is a rare form of lactic acidosis and is typically due to a genetic defect in an enzyme in the mitochondria responsible for helping the body convert carbohydrates and fats into energy. These defects are either inherited from one or both parents or arise spontaneously in the developing embryo. The enzyme deficiencies that give rise to congenital lactic acidosis can potentially affect many different organ systems of the body and, therefore, lead to a wide variety of symptoms and signs. Whereas some individuals may have persistently elevated levels of lactic acid in blood, cerebrospinal fluid and urine, other persons may have only occasional increases in lactic acid that are brought on by another illness, such as an infection, a seizure or an asthmatic attack. In some cases (especially those with a severe enzyme defect), symptoms of congenital lactic acidosis develop within the first hours or days of life and may include loss of muscle tone (hypotonia), lethargy, vomiting and abnormally rapid breathing (tachypnea). Eventually, the condition may progress to cause developmental delay, mental retardation, motor abnormalities, behavioral issues, abnormalities of the face and head and, ultimately, multi-organ failure. In some individuals in whom the disease is due to a mutation in mitochondrial DNA, the complications of congenital lactic acidosis may not appear until adolescence or adulthood. Pyruvate dehydrogenase complex (PDC) deficiency is generally considered to be the most common cause of biochemically proven cases of congenital lactic acidosis.
Although genetic mitochondrial diseases are the most common causes of congenital lactic acidosis, additional conditions that are present at birth can result in the disorder, including biotin deficiency, bacterial infection in the bloodstream or body tissues (sepsis), certain types of glycogen storage disease, Reye syndrome, short-bowel syndrome, liver failure, a defect in the heart or blood vessels that leads to a deficiency in the amount of oxygen reaching the body’s tissues (hypoxia) and bacterial meningitis (which causes elevated lactic acid in cerebrospinal fluid).
Treatment is generally symptomatic and individualized. Vitamins and certain co-factors (for example, carnitine and coenzyme Q) are frequently administered to patients with congenital lactic acidosis, but there is no proof that such agents are effective, except in extremely rare cases of PDC deficiency that respond to high doses of thiamine. For many years so-called “ketogenic” diets that are very high in fat and very low in carbohydrate have been used in patients with PDC deficiency, with beneficial effects reported in the scientific literature. Dichloroacetate (DCA) has been investigated as a potential therapy for individuals with congenital lactic acidosis. Various studies have shown the drug to be well-tolerated in children and to lead to a reduction in lactic acid levels in many patients with various causes of congenital lactic acidosis. However, the clinical benefit of chronic DCA treatment for any type of congenital lactic acidosis has not yet been demonstrated by controlled clinical trials. In addition, the drug has been shown to worsen or to cause reversible peripheral nerve damage in some individuals with congenital lactic acidosis, especially in older adolescents and adults. Recent studies, however, indicate that this potential side effect may be mitigated or prevented by careful dosing, based on a person’s particular genotype.