Phosphoglycerate kinase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Phosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major forms of the condition. The most common form is sometimes called the hemolytic form. It is characterized by a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Some people with the hemolytic form also have symptoms related to abnormal brain function, including intellectual disability, seizures, and stroke.

The other form of phosphoglycerate kinase deficiency is often called the myopathic form. It primarily affects muscles, causing progressive weakness, pain, and cramping, particularly with exercise. During exercise, muscle tissue can be broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can lead to kidney failure.

Most people with phosphoglycerate kinase deficiency have either the hemolytic form or the myopathic form. However, other combinations of signs and symptoms (such as muscle weakness with neurologic symptoms) have also been reported.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Phosphoglycerate kinase deficiency is caused by mutations in the PGK1 gene. This gene provides instructions for making an enzyme called phosphoglycerate kinase, which is involved in a critical energy-producing process in cells known as glycolysis. During glycolysis, the simple sugar glucose is broken down to produce energy.

Mutations in the PGK1 gene reduce the activity of phosphoglycerate kinase, which disrupts energy production and leads to cell damage or cell death. It is unclear why this abnormality preferentially affects red blood cells and brain cells in some people and muscle cells in others. Researchers speculate that different PGK1 gene mutations may have varying effects on the activity of phosphoglycerate kinase in different types of cells.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an X-linked recessive pattern. The PGK1 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Females with one altered PGK1 gene, however, may have some features of phosphoglycerate kinase deficiency, such as anemia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Phosphoglycerate kinase deficiency appears to be a rare disorder. About 30 families with affected members have been reported in the scientific literature.

Understanding terms used in the source

These definitions explain medical words used above. A definition is not evidence that another condition is present, and it does not predict how a symptom will develop. Ask the clinician which terms apply to the actual examination or test result.

Intellectual disability

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

X-linked inheritance

A mode of inheritance that is observed for traits related to a gene encoded on the X chromosome.

Hemolytic anemia

A type of anemia caused by premature destruction of red blood cells (hemolysis).

Progressive

Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age.

Affected

This term applies to a family member who is diagnosed with the same condition as the individual who is the primary focus of investigation (the proband).

Which doctor should you see?

The suggested department for discussing Phosphoglycerate kinase deficiency is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.