Written by Mohammed Majrashi and Edited by Myra Ali
Although most people are aware of rare blood diseases plaguing our society, some are not aware of the many different types of rare blood diseases. One such rare blood disease is Diamond-Blackfan Anemia (DBA), which occurs when bone marrow (the spongy center of bones where blood cells are made) does not produce enough red blood cells, which are cells that carry oxygen to distant organs and tissues [1]. This resulting shortage of red blood cells, called anemia, appears in the first year of life and causes DBA patients to receive an insufficient amount of oxygen at their organs and tissues, often manifesting in death of these oxygen-deprived cells [1]. Although symptoms of DBA vary from one person to the other, common symptoms include fatigue, weakness, and a pale appearance known as pallor [2]. Particular physical abnormalities are also common symptoms of DBA, such as distinct facial features (cleft palate, cleft lip), small head, short and webbed neck, small shoulder blades, hand deformities and, in some cases, short stature [3].
DBA affects approximately five to seven liveborn infants per million, and great endeavours have been made by researchers to understand the biological cause of this rare disorder [2]. Recent studies have found that DBA can arise from mutations in nine different genes (RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 ) important for making the proteins that combine together to form specific structures in cells called ribosomes [4]. Ribosomes convert the information stored within genes into functional proteins that perform various tasks within cells [1]. Normally, ribosomes consist of two separate parts: the large subunit and the small subunit [4]. The RPL5, RPL11, and RPL35A genes contain the information to make the proteins of the large subunit whereas the RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes contain the information to make the proteins of the small subunit [4]. Although the precise function of each individual protein is not currently understood, researchers have discovered that some of these proteins work to stabilize the structures of ribosomes while others work to carry out the ribosomes’ main function of building proteins [5]. A single mutation in any of these genes is typically sufficient enough for a person to develop the disease, and the mutated gene can be inherited from either parent [3]. Such a pattern of inheritance is known as autosomal dominant, meaning that the development of this disorder does not depend on which parent the mutated gene was inherited from (autosomal, or not sex-linked) and only one mutated gene is needed to cause DBA in the affected person instead of needing mutated genes from both parents (dominant) [3].
Fortunately, patients with DBA have various treatments available to them that range from managing their symptoms to curing this blood disorder. One of the most common managing treatments for DBA is to receive blood transfusions, as this replenishes the body with new and healthy red blood cells to deliver sufficient amounts of oxygen to the body’s organs and tissues [3]. As for curative treatments, one common method is for DBA patients to receive a bone marrow transplant. In this procedure, patients receive blood stem cells, which are cells capable of only developing into the different types of blood cells such as functional red blood cells. These blood stem cells are found in the donor’s bone marrow [3]. Although both of these managing and curative treatments sound very promising, they often cause secondary complications to arise. One such secondary complication arising from blood transfusions is hemochromatosis: an overaccumulation of iron in the body from the large amount of blood received, leading to organ damage. Secondary complications arising from bone marrow transplants for patients with DBA consist of different types of cancers, including leukaemia (blood cancer) and osteosarcoma (bone cancer) [3]. However, even though treatments for DBA often give rise to complications, recent studies on DBA treatments suggest that receiving pluripotent stem cells (cells capable of forming into blood cells and also many other cell types of the body) can potentially be used to genetically fix the defective ribosomal proteins arising from mutated genes [6]. As researchers continue to investigate further treatments for DBA, perhaps the insights gained from these studies may also be applied to the various other types of rare blood disorders in our near future.
References:
- “What is Diamond Blackfan Anemia?” Diamond Blackfan Anemia Foundation, INC.
- “Diamond-Blackfan Anemia.” Genetics Home Reference. U.S. National Library of Medicine.
- “Diamond-Blackfan Anemia.” Genetic and Rare Diseases Information Center.
- Farrar, J. E., Dahl, N. 2011. Untangling the phenotypic heterogeneity of Diamond Blackfan anemia. Seminars in Hematology. 48:124-135
- Boria, I., Garelli, E., Gazda, H. T., Aspesi, A., Quarello, P., Pavesi, E., etc. 2010. The ribosomal basis of diamond‐blackfan anemia: mutation and database update. Human mutation. 12:1269-1279.