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# Pyruvate dehydrogenase deficiency

Pyruvate dehydrogenase deficiency is a genetic disease in which cells cannot burn sugar properly; it mainly harms the brain.

Updated 2026-10-31

## Structures involved

Tap one to see what it is and open it in 3D.

- [Putamen](https://durgical.com/en/anatomy/putamen/)
- [Midbrain](https://durgical.com/en/anatomy/midbrain/)
- [Caudate nucleus](https://durgical.com/en/anatomy/caudate-nucleus/)
- [Cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/)
- [Thalamus](https://durgical.com/en/anatomy/thalamus/)
- [Lateral ventricles](https://durgical.com/en/anatomy/lateral-ventricle/)

## In biochemistry

- [Krebs cycle: Link (PDH) · Pyruvate dehydrogenase complex (PDH)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/#paso-0)
- [Alanine](https://durgical.com/en/biochemistry/molecules/alanine/)
- [Acetyl-CoA](https://durgical.com/en/biochemistry/molecules/acetyl-coa/)
- [Pyruvate dehydrogenase complex (PDH)](https://durgical.com/en/biochemistry/enzymes/pyruvate-dehydrogenase-complex/)

## What it is

Low activity of the pyruvate dehydrogenase complex, usually from PDHA1 variants on the X chromosome. Pyruvate cannot enter the Krebs cycle and builds up as lactate.

## Who gets it

It is one of the most common causes of congenital lactic acidosis; it affects boys and girls, with more variable pictures in girls because of X inactivation.

## Causes

- PDHA1 variants (X-linked), most of them new
- Less often: PDHB, DLAT, DLD, PDHX or the PDP1 phosphatase (autosomal recessive)

## Risk factors

- Affected siblings or a carrier mother

## Pathophysiology

Without PDH the brain, which depends on glucose, gets too little acetyl-CoA and ATP. Pyruvate is diverted to lactate and alanine. The basal ganglia and brainstem are damaged (Leigh syndrome) and brain development may be affected before birth. The lactate/pyruvate ratio stays normal because the respiratory chain works.

## Classification

- Neonatal form: severe lactic acidosis
- Infantile form: developmental delay, Leigh syndrome
- Mild form: episodic ataxia after carbohydrate-rich meals

## Symptoms and signs

- Fast breathing, lethargy and poor feeding in the newborn
- Low muscle tone and developmental delay
- Seizures
- Ataxia that worsens with fever or carbohydrates
- Abnormal eye movements

## Red flags

- Severe lactic acidosis in a newborn
- Loss of skills after an infection (a Leigh crisis)
- Irregular breathing or apneas

## Diagnosis

**Clinical**
Lactic acidosis with neurological signs, especially if it worsens with glucose.

**Tests**
Blood and spinal fluid lactate and pyruvate (normal ratio, under 20), high alanine; PDH activity in fibroblasts or lymphocytes; gene panel (PDHA1 and others).

**Imaging**
Brain MRI: symmetric basal ganglia and brainstem lesions (Leigh), absent [corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/) or cysts; spectroscopy shows a lactate peak.

## Treatment

**Lifestyle**
Ketogenic diet: supplies ketones as fuel that bypasses PDH

**Medical**
Thiamine, because some variants respond to it

**Medical**
Dichloroacetate in selected cases (inhibits PDH kinase)

**Acute**
In crises: correct acidosis and avoid large glucose loads

## Complications

- Intellectual disability
- Epilepsy
- Respiratory failure during crises

## Test yourself

Think of the answer, then tap the question to see it.

## How is the lactate/pyruvate ratio in PDH deficiency?

Normal (under 20), unlike respiratory-chain defects.

## Why is the ketogenic diet used?

Ketones enter the cycle as acetyl-CoA without going through PDH.

## Which gene causes most cases and how is it inherited?

PDHA1, X-linked.

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## Related conditions

- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)
- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Pyruvate dehydrogenase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/pyruvate-dehydrogenase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [PDHA1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/pdha1/) (MedlinePlus, US National Library of Medicine, 2026); [Leigh syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/leigh-syndrome/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/conditions/pyruvate-dehydrogenase-deficiency/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/pyruvate-dehydrogenase-deficiency/