PDH deficiency

Pyruvate dehydrogenase (PDH) deficiency is a rare, inherited metabolic condition. It affects how the body breaks down carbohydrates from food into usable energy, which particularly impacts the brain and nervous system.

What is pyruvate dehydrogenase complex deficiency?

PDH deficiency is a form of mitochondrial disease. To find out more about mitochondrial diseases, head over to our What is mitochondrial disease? page.

Every cell in the body needs energy to work properly, and much of that energy usually comes from breaking down carbohydrates such as bread, pasta, rice and sugary foods. An enzyme called PDH helps turn a substance called pyruvate into another chemical, acetyl CoA, which is then used to make energy.

In PDH deficiency, this enzyme doesn’t work as well as it should. Instead of being turned into energy, pyruvate builds up and is converted into lactic acid, leading to lactic acidosis and not enough energy, especially for the brain.

What are the symptoms of PDCD?

Symptoms often start in early life. PDH deficiency affects each child differently. Some symptoms appear soon after birth, while others become clearer over time. Many relate to energy levels and how the brain and muscles work​, and they can include:

• Developmental delay, such as sitting, standing, walking or talking later than expected​
• Low energy or fatigue, and difficulty keeping up with activities
• ​​Seizures
• Weak or floppy muscles and poor co-ordination or balance
• Feeding difficulties, nausea, vomiting or poor growth
• Breathing problems or episodes of lactic acidosis, where lactic acid builds up in the body

What causes pyruvate dehydrogenase complex deficiency?

PDH deficiency is caused by a mutation in one of several genes that carry the instructions for making parts of the PDH enzyme. The most commonly affected gene is called PDHA1; other genes such as PDHB, DLAT, PDHX, DLD and PDP1 can also be involved.​​

These gene changes can sometimes be inherited from a parent and sometimes happen ‘out of the blue’. In PDHA1‑related PDH deficiency, the most common cause, the genetic change is on the X‑chromosome; this means that some boys can be affected more severely, but both boys and girls can have PDH deficiency caused by PDHA1 changes.

The PDHA1 gene change often occurs spontaneously, but occasionally it can be inherited from the mother, who may have mild symptoms or be completely healthy. Changes in the other genes are usually inherited in an autosomal recessive way, meaning both parents carry one non‑working copy of the gene and one working copy but do not have any symptoms themselves.

How do you get a diagnosis of PDH deficiency?

Doctors may suspect PDCD if a baby or child has raised lactic acid levels in blood or in the spinal fluid and a combination of neurological symptoms such as seizures, poor muscle tone, developmental delay or feeding difficulties.​​

To confirm the diagnosis, specialists might arrange tests such as blood and sometimes spinal fluid tests to measure lactic acid and pyruvate, MRI scans of the brain, enzyme tests on skin cells and genetic testing to look for specific PDH‑related gene changes.​

Are there any treatments for pyruvate dehydrogenase deficiency?

At the moment, there’s no cure for PDH deficiency, but there is support and treatment available. Treatment focuses on managing symptoms, supporting development and helping the body use energy in the best way possible. Care is usually led by a specialist metabolic team.​​

Depending on each person’s needs, treatment may include anti‑seizure medicines, a carefully managed ketogenic or low‑carbohydrate diet and supplements such as thiamine or coenzyme Q10 to support energy production. Many children also benefit from physiotherapy, occupational therapy, speech and language therapy and other supportive care.​

Is there ongoing research into PDCD?

Understanding PDH deficiency matters. Because pyruvate dehydrogenase deficiency is so rare, there have historically been few studies and little guidance for families and clinicians. The Freya Foundation has helped to change this by supporting the first UK natural history study of PDH deficiency and collaborating on international patient‑journey guidelines with MetabERN, the European Reference Network for Hereditary Metabolic Disorders.​​

The Freya Foundation are also helping to fund a pioneering gene therapy project at UCL, alongside its ongoing work to make sure families and professionals have clear, up‑to‑date information on diagnosis, treatment and everyday management.​​

What support is available for someone living with PDH deficiency?

PDH deficiency can be a serious and sometimes life‑limiting condition, especially when symptoms start very early in life, but every case is different. Some babies become very unwell soon after birth, while children who develop symptoms later may have more time to reach milestones but are still likely to have learning and physical difficulties.​​

Living with PDCD can be challenging, but research and care are moving forward. Earlier diagnosis, tailored diets, better seizure control and co-ordinated specialist support mean many children are now living longer and fuller lives than in the past, with families finding their own ways of adapting.​

The specialist mitochondrial clinics across the UK can provide expert care including diagnosis, ongoing monitoring and symptom management. Genetic counselling is also available through NHS services to help families understand inheritance patterns and support future family planning.

The Lily Foundation understand the emotional impact of receiving a diagnosis of any form of mitochondrial disease. We exist to support affected patients and families, and as well as providing practical advice and patient advocacy, we offer access to in-person support weekends, private online communities with people facing similar challenges, virtual coffee mornings and access to counselling and emotional support. Find out more about all the mitochondrial disease support we offer.

Whether you or a loved one are newly diagnosed or have been living with PDCD for some time, our mitochondrial disease Q&A page is here to help answer any other questions you may have.

Because no one should face mitochondrial disease alone.