[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Fumarase deficiency

[Conditions](https://durgical.com/en/conditions/) · [Metabolism (biochemistry)](https://durgical.com/en/conditions/)

# Fumarase deficiency

Fumarase deficiency is a very rare genetic disease of the Krebs cycle that causes severe brain damage from birth.

Updated 2026-10-31

## Structures involved

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

- [Lateral ventricles](https://durgical.com/en/anatomy/lateral-ventricle/)
- [Cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/)
- [Third ventricle](https://durgical.com/en/anatomy/third-ventricle/)
- [Kidneys](https://durgical.com/en/anatomy/kidney/)

## In biochemistry

- [Krebs cycle: Step 7 · Fumarase (fumarate hydratase)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/#paso-7)
- [Warburg effect (aerobic glycolysis in cancer)](https://durgical.com/en/biochemistry/topics/warburg-effect/)

## What it is

Lack of fumarate hydratase (FH gene) from variants in both copies of the gene: fumarate does not become malate and is lost in the urine.

## Who gets it

Very rare; only a few dozen cases have been described worldwide.

## Causes

- Autosomal recessive inheritance, FH gene
- A single altered copy does not cause this picture but hereditary leiomyomatosis and renal cell cancer (HLRCC)

## Risk factors

- Carrier or related parents

## Pathophysiology

Without fumarase the Krebs cycle is cut and the developing brain does not get enough energy; neuronal migration and brain growth are disturbed. Stored fumarate modifies proteins and the hypoxia signal.

## Symptoms and signs

- Low muscle tone and poor feeding from birth
- Seizures
- Severe developmental delay
- Distinctive facial features and a large or small head

## Red flags

- Newborn seizures with low tone

## Diagnosis

**Clinical**
Newborn encephalopathy with brain malformations and mild acidosis.

**Tests**
Urine organic acids with very high fumarate; fumarase activity in fibroblasts or lymphocytes; FH gene testing.

**Imaging**
MRI: large ventricles, polymicrogyria, a small or absent [corpus callosum](https://durgical.com/en/anatomy/corpus-callosum/).

## Treatment

**Medical**
Supportive care: seizure control and nutrition

**Rehabilitation**
Rehabilitation therapies

**Follow-up**
Genetic counselling for the family; carriers (one copy) need [kidney](https://durgical.com/en/anatomy/kidney/) and [skin](https://durgical.com/en/anatomy/skin/) surveillance for HLRCC

## Complications

- Hard-to-control epilepsy
- Severe disability

## Test yourself

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

## Which metabolite is very high in the urine?

Fumarate.

## What does a single altered FH copy cause?

Hereditary leiomyomatosis and renal cell cancer (HLRCC).

## Which step of the cycle fails?

Step 7: fumarate + water → malate.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/fumarase-deficiency/)

## Related conditions

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

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

Sources: [Fumarase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/fumarase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [FH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/fh/) (MedlinePlus, US National Library of Medicine, 2026); [Hereditary leiomyomatosis and renal cell cancer: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/hereditary-leiomyomatosis-and-renal-cell-cancer/) (MedlinePlus, US National Library of Medicine, 2026).

[← All conditions](https://durgical.com/en/conditions/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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