Pyruvate dehydrogenase complex (PDC) deficiency

What is pyruvate dehydrogenase complex deficiency?

Pyruvate dehydrogenase complex (PDC) deficiency is a genetic condition characterised by a build-up of lactic acid in the body. It is related to the metabolic system, which is carefully balanced by many types of chemical reaction that are necessary for the body to function as usual. Due to an inherited gene defect, patients with PDC are unable to effectively break down nutrients in food to produce energy. This can result in both physical effects on the body as well as neurological symptoms (related to the brain and nervous system).

 

What causes pyruvate dehydrogenase complex deficiency?

Pyruvate dehydrogenase complex refers to a group of three enzymes which are all necessary for some of the body’s metabolic reactions. Patients with low levels of one or more of these enzymes have a PDC deficiency and as such, the usual process of converting carbohydrates, fats and proteins from food into energy is affected. As such, the body’s energy conversion process is seriously compromised and ineffective.

When the body is unable to utilise the PDC enzymes as usual, a build-up develops which eventually becomes lactic acid. This leads to lactic acidosis, where the build-up reaches a rate that can be harmful to the body, particularly the liver.

What are the symptoms of pyruvate dehydrogenase deficiency?

Signs of PDC deficiency can develop from birth into later childhood. In babies, a lower than average birth weight and some physical characteristics, such as a narrow head or prominent forehead can be signs of a PDC deficiency. Low muscle tone (hypotonia), poor feeding and fatigue can also be typical of babies born with a PDC deficiency.

In serious cases, as the child develops, the PDC deficiency may go on to cause microcephaly (a smaller than average head), blindness and delays in development. In many cases, the patient’s motor skills are also affected.

Symptoms of PDC deficiency can differ greatly from person to person. Although insufficient in all patients affected by this genetic disorder, the exact level of PDC enzymes varies from patient to patient meaning that some people experience more severe symptoms than others.

The most common symptoms that result from a build-up of lactic acid include:

nausea vomiting breathing problems abnormal heart rate

In some patients with a minor deficiency, these symptoms may only be experienced when they are otherwise unwell, under stress or when they consume large amounts of carbohydrates. They may also experience ataxia, where muscles move abnormally.

Is pyruvate dehydrogenase complex deficiency serious?

In the most serious cases with symptoms showing soon after birth, pyruvate dehydrogenase complex deficiency can be a life-threatening condition.

The outlook for children who show signs of the condition in later years of infancy is better. However, survival into adulthood is dependent on effective treatment. Neurological symptoms of the condition, such as delayed motor skills, difficulty walking and poor coordination can also worsen significantly without treatment.

How is pyruvate dehydrogenase complex deficiency diagnosed?

In patients with suspected pyruvate dehydrogenase complex deficiency, doctors will seek to determine the level of activity of the PDC enzymes to see if they are functioning as they should. They will also assess the patient’s levels of lactic acid, as an excess is indicative of the condition. Blood tests will provide this information but in some cases, tissue sampling or genetic testing may be required to provide a definitive diagnosis.

How is pyruvate dehydrogenase complex deficiency treated?

The aim of treatment for this condition is to stimulate the PDC enzymes to work as they ordinarily would, meaning the body can produce energy effectively without generating an excess of lactic acid. Regulating this process with medication will stop symptoms from worsening. For some patients, medication may also be prescribed to help prevent seizures from occurring.

To prevent lactic acidosis, a ketogenic diet, with high quantities of fats and low amounts of carbohydrates, may be prescribed. For patients with a PDC deficiency, this type of diet is more easily processed and is beneficial in managing some symptoms, but doesn’t affect the condition’s neurological effects on the body.

What type of doctor treats pyruvate dehydrogenase complex deficiency?

Specialist paediatricians, geneticists and endocrinologists treat patients with a PDC deficiency.