Decoding DBA: The truth about rare anemia in infants and young children

Author: Han Bing, Chief Physician, Peking Union Medical College Hospital

Reviewer: Jiang Qian, Chief Physician, Third Medical Center, PLA General Hospital

In the vast field of medicine, rare diseases have always attracted the attention of scientists and clinicians with their unique pathogenesis and clinical manifestations. Congenital pure red cell aplasia (DBA) is such a rare and complex genetic disease that mainly affects infants and young children and is marked by pure red cell reduction and specific clinical features.

The disease is named after Diamond and Blackfan, two foreign scholars who first reported the disease in 1938, namely Diamond-Blackfan Anemia (DBA). The main feature of the disease is anemia caused by impaired red blood cell production, while white blood cells and platelets are relatively normal.

The cause of DBA is deeply hidden in the genetic material, mainly caused by gene mutations. Specifically, these mutations affect the function of key structural proteins in the process of hemoglobin synthesis in mitochondria, making it impossible to synthesize hemoglobin precursor components normally, thereby causing anemia.

It is worth noting that about 30%-50% of DBA cases have a familial inheritance pattern, mostly autosomal dominant or recessive inheritance, and the remaining cases may be caused by new mutations. RPS19 gene mutation is the most common variation, accounting for about half of all cases. This gene is located on the short arm of chromosome 19 and the short arm of chromosome 8, and the ribosomal protein encoded by it is essential for red blood cell maturation.

In addition, environmental factors also play a role in the development of DBA. Although the specific environmental factors have not yet been fully clarified, it can be speculated that certain external conditions may aggravate or trigger the expression of gene mutations, thereby increasing the risk of disease.

The clinical manifestations of DBA are quite characteristic. First, the disease develops early, with 90% of patients showing symptoms within one year of age, manifested by anemia, low reticulocyte counts, and a lack of red blood cells in the bone marrow. In contrast, the number of white blood cells and platelets in patients is basically normal, making DBA particularly unique among blood system diseases.

In addition, patients may have special facial features, webbed necks, strabismus, growth and development abnormalities, and visceral malformations such as the heart and kidneys. It is worth noting that compared with the general population, DBA patients have a significantly increased risk of developing tumors in adulthood.

Figure 1 Original copyright image, no permission to reprint

In addition, DBA not only affects children's growth and development and organ function, but may also cause iron overload. Because anemia causes DBA patients to undergo repeated blood transfusions, and repeated blood transfusions will prevent the iron released after the decomposition of foreign red blood cells in the body from being effectively excreted, accumulating in the liver, heart, and endocrine glands, causing the "black liver" phenomenon, that is, the organs appear black in MRI images. Moreover, DBA itself causes a disorder in the iron regulation system, and the body mistakenly believes that the body is iron deficient, thereby accelerating iron absorption and further leading to iron overload. Iron overload increases the risk of cirrhosis and liver cancer, and causes heart failure, hypothyroidism, early-onset diabetes, and sexual dysfunction.

Figure 2 Original copyright image, no permission to reprint

Comprehensive clinical evaluation and laboratory tests are essential for diagnosing DBA. Doctors usually use blood routine, bone marrow puncture, chromosome and gene testing to comprehensively evaluate the patient's condition. In particular, gene testing can directly detect mutations in key genes such as RPS19, providing a strong basis for the diagnosis of DBA.

DBA has a unique anemia phenotype compared with other diseases such as transient erythrocytopenia, Pearson syndrome, Fanconi anemia, and dyskeratosis congenita. For example, ring sideroblasts are found in the bone marrow of patients with Pearson syndrome, and the genetic manifestations of Fanconi anemia and dyskeratosis congenita are significantly different from those of DBA.

Although DBA is difficult to prevent, parents should not jump to conclusions when anemia is found during routine health screening, but should pay close attention, seek timely follow-up visits, and avoid infections and adverse environmental factors during pregnancy. For couples with known family members with DBA, genetic counseling should be considered to assess the risk of disease in subsequent births. Although prenatal examinations cannot ensure the detection of DBA, regular monitoring of fetal development and organ status, as well as hemoglobin monitoring after birth and genetic testing when necessary, can help identify signs of the disease early.