Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) can be caused by mutations in the RPS19gene (25% of the cases) or in the following genes: RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24 , or RPS26 genes (25%-35% of the cases). In very rare cases, the disease is caused by a mutation in the GATA1 gene. In the remaining 40%-50% of the cases the cause is unknown.

The RPS19 , RPL5 , RPL11 , RPL35A , RPS7 , RPS10 , RPS17 , RPS24 , and RPS26 genes provide instructions for making several of the different ribosomal proteins. Ribosomes are components of cellular structure that process the cell's genetic instructions to create proteins. Each ribosome is made up of two parts (subunits) called the large and small subunits. The RPL5, RPL11 , and RPL35A genes provide instructions for making ribosomal proteins found in the large subunit. The ribosomal proteins produced from the RPS7, RPS10 , RPS17, RPS19, RPS24 , and RPS26 genes are among those found in the small subunit. Some ribosomal proteins are involved in the assembly or stability of ribosomes and others help building new proteins or have other functions. A shortage of functioning ribosomal proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia.

According to the mutated gene people may have some differences in their symptoms:

• People who have mutation in the RPL5 gene appear to have more severe problems than people with mutations in the RPL11 and RPS19 genes.
• People with mutations in the RPL5 gene have more chances of having cleft lip and/or cleft palate defects.
• People with mutations in the RPL11 gene have more thumb abnormalities
• People with mutations in the GATA1 gene may have a more severe anemia.

In about 30% of people diagnosed with Diamond-Blackfan anemia no mutation is found in any of the known DBA-linked genes.

Diamond-Blackfan anemia is most commonly inherited in an autosomal dominant manner. This means that to be affected, a person only needs a change (mutation) in one copy of the mutated gene in each cell. A person with Diamond- Blackfan anemia has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

Around 45% of affected people have inherited the mutation from a parent and about 55% have a new ( de novo) mutation, where the anemia appears for the first time in the family and there are not other cases in the family. People with Diamond-Blackfan anemia may not appear to have a family history of the condition if relatives have very mild signs and symptoms.

In rare cases, when caused by mutations in the GATA1 and in the TSR2 gene, Diamond-Blackfan anemia can be inherited in an X-linked manner. In these cases, a if a man have a mutated copy of one of these genes he will be affected; a woman who have an abnormal copy is known as "carrier" but do not have the disease. Carries have a 50% chance of transmitting the mutated copy to each of her daughters or sons in each pregnancy: All of her sons who inherit the mutated copy will have the disease and all her daughters with the mutated copy will be carriers.

The chance that a sibling will also have Diamond-Blackfan anemia depends on the underlyng inheritance pattern and whether or not the mutation has been inherited from a parent. For the majority of cases inherited in an autosomal dominant pattern, if the mutation was found in either parent, child has a 50% chance of inheriting Diamond-Blackfan anemia. Rarely, mutations are inherited in an X-linked pattern. If mutations are identified in either parent, the risk for inheritance is dependent on the sex of the parent and the child. At most, the risk would be 50%. If the mutation is not found in either parent, then the risk for a sibling to be affected is low.

Some people have such mild signs and symptoms that they do not require treatment. In people who require treatment it may include:

• Corticosteroids: Corticosteroid treatment is recommended in children over 1 year of age; this treatment can initially improve the red blood count in approximately 80% of people with Diamond-Blackfan anemia. Prednisone initial dose is 2 mg / kg / day given orally once a day, at morning time. After a month, if there is no improvement after a month the corticosteroids are tapered-of and suspended
• Blood transfusions, which are given along with the corticosteroids or in people who do not get better with corticosteroids
• Bone marrow/stem cell transplantation: It is the only curative treatment for the anemia; however, patients should continue to be followed because they are at increased risk for leukemia and cancer. Results are better for children younger than ten years of age if transplanted using an Human Leukocyte Antigen (HLA)-matched sib