Enzymatic Defects Causing Hemolysis in Children
Introduction to Enzymatic Defects Causing Hemolysis in Children
Enzymatic defects are a significant cause of hemolytic anemia in pediatric populations. These disorders result from genetic mutations affecting various enzymes involved in red blood cell (RBC) metabolism. The compromised enzymatic function leads to decreased RBC lifespan and premature destruction, manifesting as hemolysis.
Key points:
- Enzymatic defects are typically inherited in an autosomal recessive manner, with some exceptions (e.g., G6PD deficiency is X-linked).
- The most common enzymatic defects include glucose-6-phosphate dehydrogenase (G6PD) deficiency, pyruvate kinase deficiency, and hexokinase deficiency.
- Clinical presentation can vary from mild, chronic hemolysis to severe, life-threatening anemia.
- Diagnosis often requires specialized laboratory tests to evaluate enzyme activity and genetic analysis.
- Management strategies depend on the specific enzyme defect and severity of hemolysis.
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
G6PD deficiency is the most common enzymatic defect causing hemolysis, affecting over 400 million people worldwide.
Pathophysiology:
- X-linked recessive inheritance
- G6PD enzyme is crucial for protecting RBCs against oxidative stress
- Deficiency leads to increased susceptibility to oxidative damage and hemolysis
Clinical Presentation:
- Acute hemolytic episodes triggered by oxidative stress (e.g., certain medications, fava beans, infections)
- Neonatal jaundice
- Chronic hemolysis (rare)
Diagnosis:
- Quantitative G6PD enzyme activity assay
- Genetic testing for confirmation and variant identification
Management:
- Avoidance of triggering factors
- Supportive care during hemolytic episodes
- Folic acid supplementation
- Rarely, blood transfusions for severe anemia
Pyruvate Kinase (PK) Deficiency
PK deficiency is the most common glycolytic enzyme defect causing chronic hemolytic anemia.
Pathophysiology:
- Autosomal recessive inheritance
- PK enzyme catalyzes the final step of glycolysis in RBCs
- Deficiency leads to decreased ATP production and shortened RBC lifespan
Clinical Presentation:
- Neonatal jaundice
- Chronic hemolytic anemia of variable severity
- Splenomegaly
- Gallstones
Diagnosis:
- PK enzyme activity assay
- Genetic testing for PKLR gene mutations
Management:
- Folic acid supplementation
- Blood transfusions as needed
- Splenectomy in severe cases
- Iron chelation therapy for transfusion-dependent patients
- Hematopoietic stem cell transplantation in select cases
Hexokinase Deficiency
Hexokinase deficiency is a rare enzymatic defect causing hemolytic anemia.
Pathophysiology:
- Autosomal recessive inheritance
- Hexokinase catalyzes the first step of glycolysis in RBCs
- Deficiency results in decreased glucose utilization and ATP production
Clinical Presentation:
- Chronic hemolytic anemia
- Splenomegaly
- Variable severity, from mild to transfusion-dependent
Diagnosis:
- Hexokinase enzyme activity assay
- Genetic testing for HK1 gene mutations
Management:
- Folic acid supplementation
- Blood transfusions as needed
- Splenectomy in severe cases
Diagnosis and Management of Enzymatic Defects
Diagnostic Approach:
- Clinical history and physical examination
- Complete blood count (CBC) with reticulocyte count
- Peripheral blood smear examination
- Hemolysis markers (e.g., haptoglobin, LDH, bilirubin)
- Specific enzyme activity assays
- Genetic testing for confirmation and variant identification
General Management Principles:
- Folic acid supplementation to support erythropoiesis
- Avoidance of oxidative stressors in G6PD deficiency
- Monitoring for complications (e.g., gallstones, iron overload)
- Genetic counseling for affected families
- Patient and family education about the condition
Emerging Therapies:
- Gene therapy approaches for various enzymatic defects
- Novel small molecule activators for pyruvate kinase deficiency
- Mitapivat (AG-348) for pyruvate kinase deficiency
Enzymatic Defects Causing Hemolysis in Children
- Question: What is the most common enzymatic defect causing hemolysis in children? Answer: Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Question: Which enzyme deficiency is associated with chronic hemolysis and gallstones in children? Answer: Pyruvate kinase deficiency
- Question: What is the inheritance pattern of G6PD deficiency? Answer: X-linked recessive
- Question: Which population has the highest prevalence of G6PD deficiency? Answer: African and Middle Eastern populations
- Question: What is the primary function of G6PD in red blood cells? Answer: Protection against oxidative stress
- Question: Which enzyme deficiency can cause severe neonatal jaundice and chronic hemolysis? Answer: Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Question: What is the most common trigger for hemolysis in G6PD-deficient individuals? Answer: Oxidative stress (e.g., certain medications, fava beans)
- Question: Which enzyme deficiency is associated with hereditary nonspherocytic hemolytic anemia? Answer: Pyruvate kinase deficiency
- Question: What is the inheritance pattern of pyruvate kinase deficiency? Answer: Autosomal recessive
- Question: Which laboratory test is used to diagnose G6PD deficiency? Answer: Quantitative G6PD enzyme activity assay
- Question: What is the primary treatment for acute hemolytic episodes in G6PD deficiency? Answer: Supportive care and avoidance of oxidative stressors
- Question: Which enzyme deficiency can cause both hemolytic anemia and neurological symptoms? Answer: Hexokinase deficiency
- Question: What is the role of pyruvate kinase in red blood cells? Answer: ATP production through glycolysis
- Question: Which enzyme deficiency can cause hemolytic anemia and increased susceptibility to malaria? Answer: Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Question: What is the primary treatment for pyruvate kinase deficiency? Answer: Supportive care, including blood transfusions and splenectomy in severe cases
- Question: Which enzyme deficiency is associated with chronic hemolysis and reticulocytosis? Answer: Pyruvate kinase deficiency
- Question: What is the most common complication of chronic hemolysis in enzymatic defects? Answer: Gallstones (cholelithiasis)
- Question: Which enzyme deficiency can cause hemolytic anemia and methemoglobinemia? Answer: Cytochrome b5 reductase deficiency
- Question: What is the primary function of hexokinase in red blood cells? Answer: Catalyzing the first step of glycolysis
- Question: Which enzyme deficiency is associated with hereditary xerocytosis? Answer: Phosphoglycerate kinase deficiency
- Question: What is the most common clinical presentation of pyruvate kinase deficiency in infants? Answer: Neonatal jaundice and anemia
- Question: Which enzyme deficiency can cause both hemolytic anemia and myopathy? Answer: Phosphoglycerate kinase deficiency
- Question: What is the primary function of glucose-6-phosphate isomerase in red blood cells? Answer: Catalyzing the second step of glycolysis
- Question: Which enzyme deficiency is associated with chronic hemolysis and splenomegaly? Answer: Pyruvate kinase deficiency
- Question: What is the most common cause of death in severe cases of G6PD deficiency? Answer: Acute hemolytic crisis with severe anemia
- Question: Which enzyme deficiency can cause both hemolytic anemia and neuromuscular symptoms? Answer: Phosphofructokinase deficiency
- Question: What is the primary function of aldolase in red blood cells? Answer: Catalyzing the fourth step of glycolysis
- Question: Which enzyme deficiency is associated with chronic hemolysis and increased susceptibility to infections? Answer: Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Question: What is the most common complication of splenectomy in children with enzymatic defects causing hemolysis? Answer: Increased risk of infections, particularly with encapsulated bacteria
- Question: Which enzyme deficiency can cause both hemolytic anemia and mental retardation? Answer: Triosephosphate isomerase deficiency
