ĐẶT LỊCH KHÁM

Pyruvate kinase deficiency is a rare inherited disorder that can lead to chronic hemolytic anemia, jaundice, enlarged liver and spleen and many serious complications from the fetal and neonatal stages through adulthood. Understanding the causes, warning signs and the role of genetic testing can help families proactively pursue carrier screening and genetic counseling before marriage, before pregnancy or during assisted reproductive treatment.

1. What is Pyruvate Kinase Deficiency (PKD)?

Pyruvate kinase deficiency (PKD) is a rare genetic disorder characterized by the premature destruction of red blood cells, resulting in chronic hemolytic anemia. PKD is an autosomal recessive inherited disease caused by mutations in the PKLR gene, leading to deficiency of the pyruvate kinase enzyme, which plays a crucial role in red blood cell glycolysis.

Clinical manifestations vary widely, ranging from severe anemia presenting during pregnancy with hydrops fetalis to very mild cases with little or no clinical symptoms.

2. Causes of the Disease

Mutations in the PKLR gene are considered the underlying cause of PKD. This gene encodes pyruvate kinase, an enzyme essential for glycolysis in red blood cells, providing energy for cellular function and maintaining structural stability. Mutations in the PKLR gene reduce or impair pyruvate kinase enzyme activity, causing red blood cells to become fragile and leading to hemolytic anemia.

PKD is inherited in an autosomal recessive pattern, affecting males and females equally. Normally, each person carries two copies of the PKLR gene, one inherited from the father and one from the mother. The disease manifests only when an individual inherits two mutated copies of the gene. Individuals carrying only one mutated copy are considered asymptomatic carriers and do not develop the disease.

Severe forms of pyruvate kinase deficiency may lead to death shortly after birth.

Thus, if both parents are carriers, they will not show symptoms of the disease. However, with each pregnancy, their child has:

• A 25% chance of inheriting two normal genes and being completely unaffected
• A 50% chance of inheriting one normal gene and one mutated gene, becoming an asymptomatic carrier
• A 25% chance of inheriting two mutated genes and developing the disease with clinical manifestations

3. Clinical Symptoms

The clinical presentation of pyruvate kinase deficiency can vary significantly. In severe cases, symptoms may appear during fetal development or immediately after birth and may be life-threatening. In milder cases, symptoms may be subtle or even absent.

3.1. Hydrops Fetalis

In severe cases, the disease may present during pregnancy with fetal anemia leading to hydrops fetalis, including:

• Enlarged heart
• Pericardial effusion
• Ascites
• Pleural effusion
• Thickened placenta

3.2. Neonatal Anemia

Some newborns may develop severe symptoms immediately after birth, including:

• Severe jaundice, which may progress to kernicterus
• Risk of death and cerebral palsy complications
• Enlarged liver and spleen
• Pulmonary hypertension

3.3. Anemia in Older Children and Adults

The most common symptom is anemia causing fatigue, dizziness, pale skin and weakness. Other manifestations include:

• Jaundice and yellowing of the sclera
• Enlarged liver and spleen
• Gallstones due to elevated bilirubin
• Pulmonary hypertension
• Liver cirrhosis
• Reduced bone density

Episodes of acute hemolysis may occur under stress or triggering factors such as infections or pregnancy, causing symptoms to worsen. For example, parvovirus B19 infection may trigger aplastic crisis and severe anemia requiring blood transfusion.

4. Diagnosis of Pyruvate Kinase Deficiency

Diagnosis is based on characteristic clinical manifestations, detailed family history, careful clinical examination and laboratory evaluation of hemolytic anemia, including:

• Complete blood count
• Serum bilirubin
• Lactate dehydrogenase (LDH)
• Coombs test
• Specialized investigations

Pyruvate Kinase Enzyme Activity Testing

Reduced pyruvate kinase enzyme activity is one of the key diagnostic criteria for PKD. However, this test is usually available only in specialized laboratories and is not routinely performed in all healthcare facilities.

PKLR Genetic Testing

Molecular genetic testing to identify PKLR mutations is an important diagnostic standard for PKD. It helps confirm the diagnosis and distinguish PKD from other hemolytic anemias.

5. Treatment

Currently, there is no definitive cure for pyruvate kinase deficiency. Treatment mainly focuses on symptom management and improving quality of life, including:

• Phototherapy or exchange transfusion in newborns with severe hyperbilirubinemia to prevent kernicterus
• Blood transfusions for severe anemia
• Folic acid supplementation
• Iron chelation therapy for patients requiring long-term repeated transfusions
• Splenectomy
• Hematopoietic stem cell transplantation

6. Prevention

Individuals with a family history of pyruvate kinase deficiency should receive genetic counseling and undergo carrier testing to assess reproductive risks and prevent having affected children.

In addition, pre-marital, preconception and prenatal single-gene disorder screening for couples is an effective approach for early detection of carrier status, assessing disease risk in offspring and enabling timely interventions to reduce the risk of having children affected by the disease.