What is congenital pure red cell aplasia?

Congenital pure red cell aplasia is a rare congenital anemia caused by damage to erythroid progenitor cells in the bone marrow, leading to suppression of the red blood cell system.

It primarily manifests as impaired differentiation and maturation of red blood cells, while granulocyte and megakaryocyte systems remain normal. Most affected children develop symptoms within the first year of life.

First reported by Diamond and Blackfan in 1938, it is also known as Diamond-Blackfan anemia.

What causes congenital pure red cell aplasia?

Mutations or deletions in genes encoding ribosomal proteins (e.g., RPS19, RPS24, RPS17, RPL5, RPL11) lead to abnormal ribosome biogenesis, disrupting the differentiation and maturation of erythroid progenitor cells and resulting in anemia.

Who is most likely to develop congenital pure red cell aplasia?

Infants and young children, typically presenting before 1 year of age.

What are the main symptoms of congenital pure red cell aplasia?

• Bone marrow failure:

  • About 1/3 of affected infants are born with anemia, which is macrocytic or normocytic/normochromic, accompanied by reticulocytopenia, while other blood cells (granulocytes, platelets) remain normal.
  • Common manifestations include pallor, lethargy, and feeding difficulties.

• Congenital developmental abnormalities:

  • 30-50% of patients exhibit congenital malformations, primarily affecting the head, upper limbs, heart, and genitourinary system (e.g., short stature, craniofacial deformities, congenital cataracts, thumb abnormalities, cardiovascular anomalies, genitourinary malformations).

• Increased cancer susceptibility:

  • Approximately 4% of patients develop tumors, significantly higher than the general population. Common cancers include hematologic, lymphatic, and digestive system malignancies (e.g., acute leukemia, myelodysplastic syndrome, lymphoma, thymic carcinoma, hepatocellular carcinoma, melanoma, fibrohistiocytoma, gastric/colorectal cancer).
  • Prognosis is poorer with earlier onset and higher mortality compared to non-anemic patients with the same cancers.

Which department should be consulted for congenital pure red cell aplasia?

Departments: Hematology, Pediatrics.

How is congenital pure red cell aplasia diagnosed?

• Clinical manifestations.
• Blood tests, hemoglobin electrophoresis, bone marrow examination.

How is congenital pure red cell aplasia treated?

• Corticosteroids:

  • About 40% of patients are steroid-dependent and may respond to glucocorticoid therapy.

• Blood transfusions:

  • Approximately 40% are transfusion-dependent. Transfusions are the main treatment for steroid-resistant patients or those with contraindications to steroids.

• Hematopoietic stem cell transplantation (HSCT):

  • HSCT may be considered for steroid-refractory or transfusion-dependent cases. Donor genetic screening is essential to exclude pathogenic mutations.

What is the prognosis of congenital pure red cell aplasia?

• Infants may achieve remission (hemoglobin ≥80 g/L for ≥6 months without transfusions/therapy).
• Overall survival rate is 75.1% by age 40. Main causes of death include hemosiderosis, steroid-related complications (bleeding/infections), severe aplastic anemia, and malignancies.

How to prevent congenital pure red cell aplasia?

40-50% of cases follow autosomal dominant inheritance, enabling early genetic testing/intervention:

• Preconception genetic counseling and prenatal testing for family planning.
• Prevent infections (e.g., colds, injuries).
• Provide attentive care, psychological support, and a positive living environment.