Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals.

The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills, such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking.

Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many people with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.

Source taken from The Genetic Home Reference Website



Pyruvate dehydrogenase deficiency (PDH) is one of the most common neurodegenerative disorders associated with abnormal mitochondrial metabolism. The citric acid cycle is a major biochemical process that derives energy from carbohydrates. Malfunction of this cycle deprives the body of energy. An abnormal lactate buildup results in nonspecific symptoms.


Signs and Symptoms

The progression and presentation of Pyruvate dehydrogenase deficiency widely varies and affects each child differently. Below are some of the more common signs and symptoms -

  1. Developmental delay,
  2. Intermittent ataxia,
  3. Poor muscle tone,
  4. Abnormal eye movements
  5. Seizures.
  6. Severe lethargy
  7. Poor feeding
  8. Mental delays
  9. Psychomotor delays
  10. Growth retardation
  11. Microcephaly and dysmorphology
  12. Progressive neurological symptoms usually start in infancy but may be evident at birth or in later childhood


How many people have PDH?

Pyruvate dehydrogenase deficiency is a rare disorder. Several hundred cases of pyruvate dehydrogenase deficiency have been reported. Most mutations are sporadic, and the recurrence rate is very low. The true occurrence of this disorder is unknown because mild mutations of the E1 alpha enzyme subunit gene on the X chromosome may be asymptomatic, especially in females.


Individuals with neonatal-onset and infantile-onset types of pyruvate dehydrogenase deficiency usually die during the first years of life. Later childhood onset of the disease is usually, but not always, associated with survival into adulthood. All children are born with some residual enzyme activity because a complete deficiency of pyruvate dehydrogenase is incompatible with life. Infants with 15% or less pyruvate dehydrogenase activity normally do not survive the newborn period. Pyruvate dehydrogenase activity greater than 25% is associated with less severe disease and is usually characterized by poor muscle tone, balance and speech and in most cases mild psychomotor delay. Some therapies may extend the lives of individuals who are severely affected with pyruvate dehydrogenase deficiency; however, the progressive nature of the neurological deterioration results in significant morbidity.



Gender differences appear for dysfunction of the E1 alpha enzyme subunit, which is coded by the X chromosome. Females can have severe symptoms, although males are typically affected to a much greater extent. The syndrome is more common in females with pyruvate dehydrogenase deficiency. Severe lactic acidosis with early demise and Leigh syndrome are more commonly observed in males with pyruvate dehydrogenase deficiency. Progressive neurological degeneration is observed more commonly in females with pyruvate dehydrogenase deficiency.



Age of presentation varies from prenatal to early childhood and depends on the residual activity of the pyruvate dehydrogenase. Individuals with severe disease have prenatal onset with structural brain abnormalities. Moderate disease presents in infants as psychomotor delay. Individuals with less severe disease usually present in early childhood with intermittent lethargy or ataxia.



Individuals with mild deficiencies in the E1 enzyme of the pyruvate dehydrogenase  have a better prognosis than those with deficiencies in the E2 and E3 pyruvate dehydrogenase enzymes.

Prediction of prognosis is unclear because of the small number of children with pyruvate dehydrogenase deficiency studied and the large number of mutations involved. In most cases of neonatal-onset and infantile-onset of pyruvate dehydrogenase deficiency, a poor prognosis remains, even when the lactic acidosis is treated successfully. Although lactic acidosis appears to be controlled by thiamine supplementation in individuals who respond to thiamine, the neurological outcome may be poor.

In general, treatment of individuals with pyruvate dehydrogenase deficiency is most beneficial if started early. Although successful treatment is rare, some cases have been reported.

Although the recurrence rate for subsequent pregnancies is low, test future gestations for pyruvate dehydrogenasedeficiency because of the possibility of other mutations.



Treatment for individuals with this disease aims to provide relief for any symptoms and support in the care of the individual. A diet that is high in fats and low in carbohydrates so that most of the calories comes from fats can stop the build up of pyruvate that leads to acidosis this is known as the Ketogenic Diet. Some supplements may also be of benefit as they are required inassociated processes. These can include thiamine, carnitine, Coenzyme Q10 and Lipoic acid, but they do vary depending of the exact deficiency that causes pyruvate dehydrogenase deficiency. When there are high levels of lactic acid in the body, fluids with sugars and salts (electrolytes) need to be given and lactate levels should be monitored. 

To help evaluate dietary manipulations and to ensure compliance, have caregivers of children with pyruvate dehydrogenase deficiency complete a dietary log.

Advise caregivers of individuals with pyruvate dehydrogenase deficiency to always carry an informational statement that describes pyruvate dehydrogenase deficiency and the appropriate medical treatment for the disorder in an emergency setting.



Pyruvate dehydrogenase (PDH) deficiency is usually caused by a deficiency of one or more enzymes or cofactors (such as thiamine) that are needed for an important chemical reaction in the cells of the body. These enzymes or cofactors are part of the pyruvate dehydrogenase and normally convert (or aid in converting) a chemical called pyruvate to another chemical called acetyl-coenzyme A (CoA), which is one of two important chemicals the body needs to make citrate for the cells. Because pyruvate cannot be converted to acetyl-CoA, there is too much pyruvate in the cells, which then gets used to produce more lactic acid (which is toxic in large amounts) and alanine; there is also not enough citrate being made by the body. Citrate is the first step in another important group of chemical reactions called the citric acid cycle, which then cannot proceed. The body tries to make alternate pathways to produce more acetyl-CoA, but there is still not enough energy made in the body, especially in the central nervous system (CNS). The amount of energy that is deficient depends on the amount of the enzyme that is deficient. The condition is sometimes referred to as pyruvate dehydrogenase (PDH) deficiency because there is a "complex" of three enzymes normally used in the reaction; when any one or more of the enzymes needed for the above-described reaction are deficient, the condition results. The most common form of pyruvate dehydrogenase deficiency is caused by mutations in the X-linked dominant E1 alpha gene: all other causes are thought to be due to mutations in recessive genes.


What is the Ketogenic diet?

The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control (refractory) epilepsy in children and metabolic disorders. The diet forces the body to burn fats rather than carbohydrates. Normally, the carbohydrates contained in food are converted into glucose, which is then transported around the body and is particularly important in fuelling brain function.

However, if there is very little carbohydrate in the diet, the liver converts fat into fatty acids and ketone bodies. The ketone bodies pass into the brain and replace glucose as an energy source. An elevated level of ketone bodies in the blood, a state known as ketosis,

Source from Wikipedia