What is PDH deficiency?

A genetic change, not something anyone caused

PDH deficiency is caused by a change (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.

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.​​

• 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 coordination or balance.​​
• Feeding difficulties, nausea, vomiting or poor growth.​​
• Breathing problems or episodes of lactic acidosis, where lactic acid builds up in the body.​​

Piecing together the clues

Doctors may suspect PDH deficiency 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.​

There is no cure yet, but there is support

At the moment, there is no cure for PDH deficiency. 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.​

Every child’s journey is different

PDH deficiency can be a serious and sometimes life‑limiting condition, especially when symptoms start very early in life. 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.​​

Research and care are moving forward. Earlier diagnosis, tailored diets, better seizure control and coordinated specialist support mean many children are now living longer and fuller lives than in the past, with families finding their own rhythms, joys and ways of adapting.​

Why understanding PDH deficiency matters

Because PDH 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 charity is 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.​​