Alpha Thalassaemia

About Alpha Thalassaemia

• Inherited genetic disorder causing reduced production of alpha-globin chains.
• Problems may arise before birth as fetal haemoglobin requires alpha chains.
• Manifestations depend on the number of absent or mutated alpha-globin genes (out of four).

Epidemiology

• More prevalent in African, Middle Eastern, Indian, Southeast Asian, and Mediterranean populations.

🧬 Aetiology

• Haemoglobin (Hb) in adults is composed of two alpha chains and two beta chains.
• Alpha Thalassaemia results from deletions or mutations in the alpha-globin genes.
• Each person has four alpha-globin genes (two from each parent).

Clinical Phenotypes

• Silent Carrier (One Gene Deletion): Asymptomatic with slight microcytosis; typically undetected without genetic testing.
• Alpha Thalassaemia Trait (Two Gene Deletions):
  • Mild microcytic anaemia without significant symptoms.
  • No splenomegaly or significant health issues.
• Haemoglobin H Disease (Three Gene Deletions):
  • Moderate microcytic, hypochromic anaemia (Hb levels 8–10 g/dL).
  • Symptoms include splenomegaly, jaundice, leg ulcers, and fatigue.
  • May worsen during pregnancy, infection, or oxidative stress.
• Hydrops Fetalis (Four Gene Deletions):
  • Not compatible with life; leads to intrauterine death or stillbirth.
  • Common cause of stillbirths in Southeast Asian countries.
• Mental learning and cognitive issues may be seen in rare variants of the disease.

🔎 Investigations

• Full Blood Count (FBC): Microcytic anaemia with low mean corpuscular volume (MCV).
• Blood Film: Shows microcytosis, anisocytosis (varying sizes), and poikilocytosis (abnormal shapes).
• Haemolysis Markers: Elevated reticulocyte count, lactate dehydrogenase (LDH), and low haptoglobin levels indicate haemolysis.
• Haemoglobin Electrophoresis: May show presence of HbH (beta tetramers) in HbH disease.
• Genetic Testing: Confirms deletions or mutations in alpha-globin genes.

💊 Management

• Haemoglobin H Disease:
  • Periodic blood transfusions may be necessary during periods of stress, infection, or pregnancy.
  • Folic acid supplementation, especially during pregnancy, to support red blood cell production.
  • Avoid oxidative drugs and substances that can precipitate haemolysis.
• Genetic Counselling: Essential for affected individuals and carriers, especially for family planning.
• Prenatal Diagnosis: Offered to at-risk couples to detect severe forms like hydrops fetalis.
• Splenectomy: Considered in cases with significant splenomegaly or frequent transfusions.

References

• NHS UK: Thalassaemia
• GeneReviews®: Alpha-Thalassemia
• World Health Organization: Genes and Human Disease

🧑‍⚕️ Case Examples - Alpha Thalassaemia

• Case 1 (Silent Carrier): 🧬 A 25-year-old man of Mediterranean origin is found incidentally to have microcytosis (MCV 74 fL) on routine bloods. Hb is normal and he feels well. Iron studies are normal. Genetic testing reveals a single alpha-globin gene deletion. Diagnosis: Alpha thalassaemia silent carrier. Management: No treatment required, but genetic counselling offered for future family planning.
• Case 2 (HbH Disease - Three Gene Deletions): 🩸 A 32-year-old pregnant woman from Southeast Asia presents with fatigue and mild jaundice. FBC: Hb 9 g/dL, MCV 68 fL. Blood film shows microcytosis and Heinz bodies. Hb electrophoresis confirms HbH (β4 tetramers). Diagnosis: Haemoglobin H disease. Management: Supportive care with folic acid, avoidance of oxidative drugs, and transfusion arranged during pregnancy when anaemia worsens.
• Case 3 (Hydrops Fetalis - Four Gene Deletions): 👶⚠️ A couple of Southeast Asian origin undergo prenatal ultrasound at 24 weeks, which shows severe fetal hydrops with hepatosplenomegaly and ascites. Genetic testing reveals homozygous alpha-thalassaemia major (–/–). Diagnosis: Hydrops fetalis due to alpha-thalassaemia major. Management: Counselling provided; parents opt for termination as prognosis is incompatible with life.