Diamond Blackfan Anemia_J. Lovett_ Presentation

DiamonD Blackfan Anemia

Jayetta Lovett

Genetics and Mutations

How is DBA inherited?

Symptoms and Treatments

DBA is an inherited blood disorder that affects the ability of the bone marrow to produce red blood cells. This impacts the ability of the body to circulate oxygen.

A visual representation of the genes involved in DBA,

A visual display of the physical effects of DBA.

Ribosomes in DBA

Lifespan of individuals with DBA

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An illustration of autosomal dominat inheritance .

An illistration of a ribosomal structure.

A image of an infant female with DBA.

A visual explaination of how DBA affects the bone marrow.

• Click here for references

A image of an infant male affected by DBA.

*Diamond Blackfan Anemia is an autosomal dominant disease. * Autosomal dominant means that to be affected, a person only needs a mutation to occur in only one copy of the mutated gene in each cell.

In the United States, 4-6 million live births per year are impacted by the DBA disease. There are approximately 25-35 new patients born per year in the USA. Worldwide, there are approximately 5000+ cases of the DBA disease.

The normal function of ribosomes is to process the genetic instructions to create proteins. In DBA, the function of the ribosome is altered. Individuals with DBA have abnormal pre-rRNA maturation and other mutations in one of the ribosomal protein genes. This mutation causes the ribosome to lack structural components that are essential for the assembly of ribosomal subunits.

The lifespan of DBA patient's with Treatment:

• Among DBA cases, 72% of them had remission within the first 10 years of life, and the majority have remission maintained, and 20% of DBA cases have remission by the age of 25 years.
• Donors: 73% survival for matched sibling donors at 5 years, compared with 17% for unrelated donors.

The life expectancy for DBA patients without treatment:

• The lifespan of individuals who have DBA with no treatment would depend on the severity of their mutation and other health-related conditions.

Genetics and Mutations

• The Mutated Genes Involved in DBA:

• RPS19: seen in 25% of patients

• RPL5: seen in 7% of patients
• RPL11: seen in 5% of patients
• RPL35a: seen in 3% of patients
• RPS26: seen in 3-6% of patients
• RPS24: seen in 2% of patients
• RPS17: seen in 1% of patients
• RPS7: seen in 1% of patients
• RPS10: seen in 3-6% of patients
• RPL19: unknown
• RPL26: unknown
• RPS29:unknown
• RPL31: unknown
• GATA1: unknown

• The RPS19 gene provides instructions for making one of approximately 80 different ribosomal proteins, which are components of cellular structures called ribosomes. Ribosomes process the cell's genetic instructions to create proteins.

• In DBA, the RPS19 gene is altered by various missense mutations such as c.3G> , a missense mutation of exon 2 resulting in p.Met1Ile, . The point mutations involved causes RPS19 to not be able to make ribosomal proteins that are needed in the human body.

Chromosome 19 is where the RPS19 gene is located. (19q13.2)

Symptoms and Treatments

Symptoms Treatment Plans

What are the symptoms of Diamond Blackfan Anemia?

• The anemia deficiency involved in DBA may cause (sometimes) white blood cells and platelets to be lower. Other symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness.

• DBA also causes physical abnormalities such as small head size (also known as microcephaly) characteristic facial features, cleft palate, cleft lip, short and webbed neck, small shoulder blades, and defects of the hands.

• Corticosteroid drugs- helps make bone marrow produce more red blood cells.

• Blood transfusion- Whole blood or red blood cells from a healthy donor can take the place of the blood cells in the body of DBA affected patient's.

• Bone marrow/stem cell transplant. This treatment replaces damaged bone marrow with healthy stem cells from a donor. It is the only cure for DBA.

What are some treatments to help with the symptoms listed?

References

• Chae, H., Park, J., Kim, M., Lim, J., Kim, Y., Han, K., Lee, J., Chung, N. G., Cho, B., & Kim, H. K. (2010). The Korean journal of laboratory medicine, 30(3), 249–254. https://doi.org/10.3343/kjlm.2010.30.3.249

• Flygare, J., Aspesi, A., Bailey, J. C., Miyake, K., Caffrey, J. M., Karlsson, S., & Ellis, S. R. (2007). Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood, 109(3), 980–986. https://doi.org/10.1182/blood-2006-07-038232

• Jahan, D., Al Hasan, M. M., & Haque, M. (2020). Diamond-Blackfan anemia with mutation in RPS19: A case report and an overview of published pieces of literature. Journal of pharmacy & bioallied sciences, 12(2), 163–170. https://doi.org/10.4103/jpbs.JPBS_234_19

• Mara Angelini, Stefano Cannata, Valentina Mercaldo, Luisa Gibello, Claudio Santoro, Irma Dianzani, Fabrizio Loreni, Missense mutations associated with Diamond–Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome, Human Molecular Genetics, Volume 16, Issue 14, 15 July 2007, Pages 1720–1727

• Muir, C., Dodds, A., & Samaras, K. (2017). Mid-life extra-haematopoetic manifestations of Diamond-Blackfan anaemia. Endocrinology, diabetes & metabolism case reports, 2017, 16-0141. https://doi.org/10.1530/EDM-16-0141

• Rarediseases.info.nih.gov. 2017. Diamond-Blackfan anemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. [online] Available at: <https://rarediseases.info.nih.gov/diseases/6274/diamond-blackfan-anemia> [Accessed 17 November 2021].

• Vlachos, A., & Muir, E. (2010). How I treat Diamond-Blackfan anemia. Blood, 116(19), 3715–3723. https://doi.org/10.1182/blood-2010-02-251090