Pyruvate dehydrogenase E3 deficiency is a rare genetic disorder that affects the body's ability to break down certain proteins and fats. It is caused by a mutation in the gene that codes for the enzyme pyruvate dehydrogenase E3 (PDHE3). This enzyme is responsible for converting pyruvate, a molecule produced during the breakdown of carbohydrates, into acetyl-CoA, which is then used in the Krebs cycle to produce energy. Without PDHE3, pyruvate accumulates in the body, leading to a variety of symptoms including seizures, developmental delays, and movement disorders. Treatment typically involves dietary modifications and supplementation with certain vitamins and minerals.

The symptoms of Pyruvate dehydrogenase E3 deficiency can vary from person to person, but may include:

-Developmental delay
-Seizures
-Movement disorders
-Muscle weakness
-Poor coordination
-Feeding difficulties
-Growth failure
-Lactic acidosis
-Hypoglycemia
-Hyperammonemia
-Neurological problems
-Cardiac arrhythmias
-Respiratory problems
-Hepatic dysfunction
-Gastrointestinal problems
-Kidney dysfunction
-Visual impairment
-Hearing loss

Pyruvate dehydrogenase E3 deficiency is caused by mutations in the PDHA1 gene, which provides instructions for making a component of the pyruvate dehydrogenase complex. This complex is responsible for converting pyruvate, a molecule derived from the breakdown of carbohydrates, into acetyl-CoA, which is used in the Krebs cycle to generate energy. Mutations in the PDHA1 gene can lead to a decrease in the activity of the pyruvate dehydrogenase complex, resulting in a buildup of pyruvate and other molecules in the body. This can lead to a variety of symptoms, including seizures, developmental delays, and movement disorders.

The primary treatment for pyruvate dehydrogenase E3 deficiency is a low-protein, low-carbohydrate diet. This diet helps to reduce the amount of pyruvate in the body, which can help reduce symptoms. Other treatments may include vitamin and mineral supplements, medications to reduce seizures, and physical therapy. In some cases, a liver transplant may be necessary.

1. Genetic mutations: Pyruvate dehydrogenase E3 deficiency is caused by mutations in the PDHA1, PDHB, and DLD genes.

2. Family history: Pyruvate dehydrogenase E3 deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

3. Ethnicity: Pyruvate dehydrogenase E3 deficiency is more common in certain ethnic groups, including Ashkenazi Jews, French Canadians, and Amish.

At this time, there is no cure for pyruvate dehydrogenase E3 deficiency. However, there are medications that can help manage the symptoms of the condition. These medications include anticonvulsants, carnitine supplements, and biotin supplements. Additionally, a low-protein diet may be recommended to help reduce the symptoms of the condition.