Makindo Medical Notes

Related Subjects: | Alpha Thalassaemia | Acute Promyelocytic Leukaemia | Acute Myeloblastic Leukaemia (AML)

A cause of microcytic anaemia.

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