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# Pyruvate kinase deficiency

Pyruvate kinase deficiency is an inherited disease in which red blood cells cannot make enough energy and are destroyed too early.

Updated 2026-10-31

## Structures involved

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

- [Spleen](https://durgical.com/en/anatomy/spleen/)
- [Liver](https://durgical.com/en/anatomy/liver/)
- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Pancreas](https://durgical.com/en/anatomy/pancreas/)

## In biochemistry

- [Glycolysis: Step 10 · Pyruvate kinase](https://durgical.com/en/biochemistry/pathways/glycolysis/#paso-10)
- [Pyruvate kinase](https://durgical.com/en/biochemistry/enzymes/pyruvate-kinase/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)

## In physiology

- [The red cell life cycle and the spleen](https://durgical.com/en/physiology/the-red-cell-life-cycle-and-the-spleen/)

## What it is

Chronic hemolytic anemia due to low activity of red-cell pyruvate kinase (PKLR gene). It is the glycolysis enzyme defect that most often causes hemolysis.

## Who gets it

It is rare, but after G6PD deficiency it is the most common enzyme cause of non-spherocytic hemolytic anemia; it is more frequent where parents are related.

## Causes

- Autosomal recessive inheritance: two PKLR variants, one from each parent
- Hundreds of variants are known; severity depends on the combination

## Risk factors

- Carrier parents or parents related to each other
- Siblings with the disease

## Pathophysiology

Without pyruvate kinase the red cell, which has only glycolysis, makes little ATP. It loses its ion pump and flexibility, dehydrates and is removed by the spleen. 2,3-BPG piles up above the block, shifting the hemoglobin curve right and improving oxygen delivery.

## Symptoms and signs

- Pallor and tiredness from anemia, mild to severe
- Jaundice (yellow eyes and [skin](https://durgical.com/en/anatomy/skin/))
- Enlarged spleen (splenomegaly)
- Severe newborn jaundice, which may need an exchange transfusion
- Gallstones at a young age

## Red flags

- A sudden fall in hemoglobin with an infection (parvovirus B19 aplastic crisis)
- Abdominal pain with fever or worsening jaundice (cholecystitis or [bile duct](https://durgical.com/en/anatomy/bile-duct/) stones)
- Signs of iron overload even without transfusions

## Diagnosis

**Clinical**
Chronic Coombs-negative hemolytic anemia without spherocytes on the smear and a recessive family pattern.

**Tests**
Blood count with high reticulocytes, raised indirect bilirubin and LDH, low haptoglobin; red-cell pyruvate kinase activity (read with care after a transfusion) and PKLR genetic testing. Ferritin to watch iron.

**Imaging**
Abdominal ultrasound to size the [spleen](https://durgical.com/en/anatomy/spleen/) and look for gallstones; MRI to measure iron in the [liver](https://durgical.com/en/anatomy/liver/).

## Treatment

**Medical**
Folic acid and transfusions according to anemia and symptoms

**Medical**
Mitapivat, an oral pyruvate kinase activator, in adults with responsive variants

**Medical**
Iron chelation when iron overload is present

**Surgical**
Splenectomy in heavily transfused cases; cholecystectomy if there are gallstones

## Complications

- Iron overload (from hemolysis and transfusions)
- Pigment gallstones
- Thrombosis and severe infections after splenectomy

## Prognosis

Highly variable: from mild forms found in adults to severe anemia needing transfusions from childhood.

## Test yourself

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

## Why does pyruvate kinase deficiency mainly affect red cells?

Red cells have no mitochondria: glycolysis is their only ATP source.

## How is 2,3-BPG in this deficiency and what does it do?

High: it shifts the hemoglobin curve right and improves oxygen delivery.

## How is it inherited?

Autosomal recessive, through PKLR variants.

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## Related conditions

- [Iron deficiency anaemia](https://durgical.com/en/conditions/iron-deficiency-anaemia/)

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

Sources: [Pyruvate kinase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/pyruvate-kinase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [PKLR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/pklr/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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