Diamond-Blackfan Anemia

The disorder Diamond-Blackfan anemia primarily affects the bone marrow. Physical abnormalities affecting numerous sections of the body are common in people with this illness.

Bone marrow’s primary purpose is to manufacture new blood cells. The bone marrow malfunctions in Diamond-Blackfan anemia, resulting in a deficiency of red blood cells to supply oxygen to the body’s tissues. Anemia (a lack of red blood cells) frequently manifests itself within the first year of life. Fatigue, weakness, and an unusually pale look are all signs of anemia (pallor).

Diamond-Blackfan anemia patients are at a higher risk of developing a number of significant consequences as a result of their faulty bone marrow. They have a higher-than-average risk of developing myelodysplastic syndrome (MDS), a condition in which immature blood cells do not develop normally. A person with Diamond-Blackfan anemia is more likely to develop a bone marrow cancer called acute myeloid leukemia (AML), a type of bone cancer known as osteosarcoma, and other cancers.

Physical abnormalities affect about half of people with Diamond-Blackfan anemia. They may have a small head (microcephaly) and a short frontal hairline, as well as distinctive facial features like wide-set eyes (hypertelorism), droopy eyelids (ptosis), a broad, flat bridge of the nose, small, low-set ears, and a small lower jaw (micrognathia). Affected people may also have a cleft palate (an opening in the roof of the mouth) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck, smaller and higher shoulder blades than normal, and anomalies in their hands, the most common of which are deformed or nonexistent thumbs. A third of those affected experience slowed growth, resulting in short height.

Other symptoms of Diamond-Blackfan anemia include clouding of the eyes’ lens (cataracts), increased pressure in the eyes (glaucoma), and eyes that don’t look in the same direction (strabismus). Kidney abnormalities, heart structural defects, and, in males, the opening of the urethra on the underside of the penis are all possible symptoms (hypospadias).

Even within the same family, the degree of Diamond-Blackfan anemia can vary. Individuals with “non-classical” Diamond-Blackfan anemia are becoming more common. The symptoms of this type of disease are usually milder. Some affected people, for example, develop moderate anemia later in childhood or age, while others have some of the physical symptoms but no bone marrow abnormalities.

Causes of Diamond-Blackfan anemia

Mutations in the RPL5, RPL11, RPL35A, RPS10, RPS17, RPS19, RPS24, and RPS26 genes, among others, can cause Diamond-Blackfan anaemia. These and other Diamond-Blackfan anaemia genes code for ribosomal proteins, which are components of cellular structures known as ribosomes. Ribosomes create proteins by processing the genetic instructions of the cell.

The large and small subunits of each ribosome are made up of two parts (subunits). The RPL5, RPL11, and RPL35A genes produce ribosomal proteins that are found in the large subunit. The RPS10, RPS17, RPS19, RPS24, and RPS26 genes produce proteins that are found in the small subunit.

Ribosome formation and stability are aided by some ribosomal proteins. Others assist in the ribosome’s primary role of protein synthesis. Some ribosomal proteins may also play other roles in the cell, such as participating in chemical signalling pathways, regulating cell division, and managing cell self-destruction, according to research (apoptosis).

RPS19 gene mutations are seen in about a quarter of those with Diamond-Blackfan anaemia. RPL5, RPL11, RPL35A, RPS10, RPS17, RPS24, or RPS26 gene mutations affect additional 25 to 35 percent of people with this condition. Ribosome dysfunction is thought to be caused by mutations in any of these genes. Anemia is thought to be caused by a lack of functioning ribosomes, which causes self-destruction of blood-forming cells in the bone marrow. Other health problems associated with Diamond-Blackfan anaemia may be caused by abnormal cell division regulation or inappropriate apoptosis triggering. Scientists are trying to figure out why blood abnormalities and health disorders differ so greatly from person to person.

The remaining Diamond-Blackfan anaemia cases are caused by mutations in a variety of different genes, some of which have yet to be found. While most cases of Diamond-Blackfan anaemia are caused by mutations in genes that supply instructions for ribosomal proteins, gene alterations affecting proteins that interact with ribosomal proteins or play other roles in blood-forming processes have been identified in a few people with this illness.

Diagnosis of Diamond Blackfan anemia

The average age of presenting with anemia is two months and the average age of diagnosis with DBA is 3-4 months. Some tests that aid in diagnosing DBA are:

complete blood count (CBC)
- values for the number of red blood cells, white blood cells, and platelets in a blood sample.
reticulocyte count (retic)
- Number of immature or young red blood cells; is given as a percentage.
mean corpuscular volume (MCV)
- The MCV is a measure of the size of the red blood cells and is found as part of the CBC. The MCV is increased for age in patients with DBA.
erythrocyte adenosine deaminase (eADA) activity level
- Elevated eADA levels are present in approximately 80-85% of patients with DBA.
genetic testing
- Genetic testing can identify a mutation in approximately 80-85% of patients with DBA.

Treatment of Diamond-Blackfan anemia

Some people’s indications and symptoms are so little that they don’t need to be treated. It may involve the following in those who require treatment: [3] \sCorticosteroids: In children above the age of one year, corticosteroid medication is advised; this treatment can improve the red blood count in about 80% of patients with Diamond-Blackfan anaemia at first. Prednisone is administered orally once a day, in the morning, at a dose of 2 mg/kg/day. If no improvement is seen after a month, the corticosteroids are tapered off and suspended.
Blood transfusions are used in conjunction with corticosteroids or in persons who do not respond to corticosteroids.

Bone marrow transplant: It is the only treatment for anaemia that is curative; however, patients should be monitored because they are at an elevated risk of leukaemia and malignancy. When a youngster under the age of ten years old is transplanted with an HLA-matched sibling, the results are better.

Related disorders

The following illnesses have symptoms that are similar to DBA. For a differential diagnosis, comparisons can be informative.

Aplastic anaemia is defined by the failure of the bone marrow. Aplastic anaemia is characterised by complete suppression or aplasia of the bone marrow. The illness could develop for unknown reasons, or as a result of an infection or a toxic reaction to radiation, medications, or chemicals. This illness can be caused by a tumour in the thymus in rare situations. Hypoplastic and aplastic bone marrow are two types of bone marrow. Hypoplasia occurs when the bone marrow is damaged or only partially functional, and aplasia happens when the bone marrow stops producing new blood cells.

Another rare genetic bone marrow failure condition is Fanconi anaemia. Congenital defects such as bone abnormalities, small head size, small genitalia, and abnormal skin colouring characterise it. Low white blood counts can lead to illnesses including pneumonia and meningitis, as well as low platelet counts, which can cause irregular bleeding. These patients are at an increased risk of contracting leukaemia and other malignancies.

(Use the search phrases “aplastic” and “Fanconi” in the Rare Disease Database to learn more about these conditions.)