Phosphoglycerate Kinase (PGK) Deficiency

What else is it called?

  • PGK deficiency
  • Phosphoglycerate kinase 1 deficiency
  • PGK1 deficiency

Get in touch

Contact our caring team on 08452 412 173 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Prefer to email? Our email address is contact@metabolicsupportuk.org.

What causes it?

This disorder is caused by a problem in the PGK1 gene. This gene provides instructions for the enzyme Phosphoglycerate kinase which is part of the process known as glycolysis. This process is needed for the breakdown of glucose which produces essential energy for the body.

If you have a problem in the PGK1 gene, you will not produce enough of the Phosphoglycerate kinase enzyme. Therefore, energy production in the body will be disrupted, which can lead to cell damage or death within the body.

 

How common is it?

PGK deficiency is extremely rare, with only 30 families with affected members having been reported.

What are the signs and symptoms?

Development of symptoms can occur at any age from childhood to adulthood within PGK deficiency. There are three main characteristics of the condition, of which patients may be affected by one or two, very rarely three; anaemia, myopathy (muscle problems) and intellectual disability.

Chronic haemolytic anaemia causes the premature breakdown of red blood cells. The symptoms include:

  • Pale skin
  • Yellowing of the eyes and skin (jaundice)
  • Fatigue
  • Shortness of breath
  • Rapid heart rate

Myopathy primarily affects muscles and the symptoms are typically heightened during periods of exercise. The main symptoms are:

  • Exercise intolerance
  • Muscle weakness
  • Cramping
  • Myalgia (pain in the muscles)
  • Myoglobinuria (presence of the protein Myoglobin in the urine) which if untreated can lead to kidney failure.

Rhabdomyolysis, the destruction of striated muscle cells has been observed in a rare few of the myopathic form.

Intellectual disability is the final characteristic of PGK deficiency and it can be seen against central nervous system manifestations, of which the symptoms are:

  • Intellectual deficit
  • Hemiplegic migraines
  • Epilepsy
  • Ataxia
  • Tremors

Due to its rarity, there is no definite life expectancy for those who live with PGK deficiency.

How is it diagnosed?

Alongside the presentation of clinical symptoms, biochemical tests that show a red blood cell count in the blood and low PGK enzyme activity within the muscle can confirm a diagnosis of PGK deficiency. Genetic testing can be done to identify the PGK1 mutation, but this may not always be necessary for a definitive diagnosis,

Currently PGK deficiency is not tested for in any newborn screening in the UK or abroad.

Can it be treated?

Unfortunately, there is no one clear cure for PGK deficiency with prognosis of patients being variable depending on the extent of the manifestations. Those who develop chronic haemolytic anaemia severely, may require regular blood transfusions. In some cases, a splenectomy (removal of the spleen) has been shown to be beneficial.

To help with myopathic symptoms, strenuous activity must be avoided to prevent exercise induced muscle fatigue and myalgia.

In cases of the most severe neurological deterioration, a bone marrow transplant may be necessary.

Do my family need to be tested?

PGK deficiency is an X-linked recessive disorder. This means that the mutation is carried on the X Chromosome, of which women have two and men only have one.

For men to develop PGK deficiency, they must have inherited the mutation on their singular X chromosome, whereas women must inherit the mutation on both copies of their X chromosome. If only one copy is inherited, they are classed as carriers. Men cannot be carriers as they either have the disease or do not.

However, even if women are carriers, in some cases they may develop some of the characteristics of PGK deficiency such as anaemia.

A carrier mother who has a son has a 50% chance of her child being unaffected or affected, and if they have a daughter, a 50% chance of her daughter being unaffected or a carrier.

A carrier father who has a son as mentioned before, will not pass on the disorder, but his daughters will all be carriers.

If two carriers have children, a son will either be affected or unaffected and a daughter will either be affected or a carrier.

It is wise to test your family if you have been diagnosed as it can identify carriers or diagnose those who have yet to develop symptoms. Identifying carriers can also assist in family planning.

Image 1 and 2: diagrams showing inheritance patterns in X-linked recessive inheritance disorders when one parent is a carrier.

Relevant Organisations

References

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing helen@metabolicsupportuk.org [Resource Library No: AAP002].

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