Pyruvate Dehydrogenase Deficiency

What else is it called?

  • Pyruvate dehydrogenase complex deficiency
  • PDHC
  • PDH deficiency
  • PDC deficiency

Get in touch

Contact our caring team on 08452 412 173 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Prefer to email? Our email address is contact@metabolicsupportuk.org.

What causes it?

Pyruvate dehydrogenase deficiency (PDD) is a type of metabolic disease. This means that the body is not able to efficiently break down nutrients in food to be used for energy.

The genes involved in pyruvate dehydrogenase deficiency each provide instructions for making a protein that belongs to a group of proteins called the pyruvate dehydrogenase complex. This complex plays an important role in the pathways that convert the energy from the food you eat, into a form that the cells in your body can use.

The pyruvate dehydrogenase complex is made up of multiple copies of several enzymes called E1, E2, and E3, each of which performs part of the chemical reaction that converts energy from food.

This disorder can be caused by a faulty version of: PDHA1, PDHB, DLAT, PDP1 etc.

How common is it?

This disorder is very rare. It is thought to affect less than 1 person in every 1,000,000

What are the signs and symptoms?

Most commonly, babies develop symptoms soon after birth. Babies may have high levels of lactate in the bloodstream (lactic acidosis). Some babies with severe lactic acidosis may have high levels of ammonia in the blood (hyperammonaemia)

Other symptoms of PDC deficiency can include:

  • Having low muscle tone (hypotonia),
  • Poor feeding,
  • Extreme tiredness (lethargy),
  • Rapid breathing (tachypnoea)
  • Abnormal eye movements
  • Seizures

Symptoms that later develop may include:

  • having a small head (microcephaly)
  • intellectual disability
  • blindness
  • tight muscles (spasticity).

80%-99% of people have these symptoms

  • Feeding difficulties in infancy
  • Lethargy
  • Low or weak muscle tone (Muscular hypotonia)

30%-79% of people have these symptoms

  • Abnormality of eye movement
  • Tremors
  • Seizures
  • Involuntary muscle stiffness, contraction, or spasm (Spasticity)
  • Abnormally small skull (Microcephaly)

5%-29% of people have these symptoms

  • Trouble breathing (Dyspnoea)
  • Multiple fatty lumps (Multiple lipomas)
  • Prominent eye folds (Epicanthus)

1%-4% of people have these symptoms

  • Visibly facial shape

How is it diagnosed?

PDD is suspected in people who have lactic acidosis or signs of early-onset neurological disease such as seizures, lethargy, and poor feeding. A doctor may wish to order more tests including:

  • Brain MRI to check for brain damage
  • Blood test to measure levels of lactic acid or pyruvate
  • Tests to measure levels of lactic acid or pyruvate in the fluid surrounding the brain and spinal cord (cerebrospinal fluid)
  • Blood test or urine test to analyse levels of the amino acid alanine

A diagnosis of PDC deficiency can be confirmed by testing the activity of the pyruvate dehydrogenase complex and the activity of all of the specific enzymes within the complex. This can be completed by sampling the blood, skin (fibroblast), or muscle. Genetic testing may be used to confirm the diagnosis.

Can it be treated?

There is no cure for this disorder. Treatment aims to stimulate the enzyme that breaks down the food to create energy to produce as much energy as possible. This can prevent immediate worsening of the disease.

Treatment options typically include supplementing substances in the body that help the chemical reactions in the cells occur. This may include cofactors including carnitine, thiamine, and lipoic acid.

A medication called dichloroacetate may help treat some people with PDC deficiency. Doctors may also recommend a diet that is high in fats and low in carbohydrates (ketogenic diet). This can help prevent lactic acidosis but typically does not stop neurological symptoms. Any dietary changes must be made following the advice of your specialist dietitian.

Medications to help prevent seizures may be recommended for some people with PDC deficiency.

Do my family need to be tested?

Due to the complexity of this disorder, this disorder can be inherited either by Autosomal recessive inheritance or by X-Linked dominant recessive inheritance, depending on the type of fault and which gene has the fault.

PDHA1 is inherited by an X-Linked inheritance

PDHB, DLAT, PDHX, DLD, and PDP1 are all inherited by autosomal recessive inheritance.

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

  • 25% chance (1 in 4) of PDHB, DLAT, PDHX, DLD, and PDP1
  • 50% chance (1 in 2) for the baby to be a carrier of PDHB, DLAT, PDHX, DLD, and PDP1
  • 25% chance (1 in 4) for the baby to have two working genes and neither have PDHB, DLAT, PDHX, DLD, and PDP1 or be a carrier

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002].

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