Pediatric blood disorders are a group of noncancerous diseases, including bone marrow failure syndromes and hemoglobinopathies, which can affect the functioning and quality of life of infants, children, and adults. In some cases, these disorders can be life-threatening.
Bone marrow failure syndromes are rare and involve low blood counts due to problems with the bone marrow – the tissue inside bones that produces hematopoietic stem cells. Hematopoietic stem cells are the parent cells of all blood cells, giving rise to oxygen-rich red blood cells, infection-fighting white blood cells, and blood clot-forming platelets that help stop bleeding. The failure of a child’s bone marrow to produce certain blood cells can be inherited through mutations (changes) in genes, or it can be acquired during a child’s lifetime.
Hemoglobinopathies are blood disorders that occur much more frequently than bone marrow failure syndromes and are inherited. They are caused by defects in a protein in red blood cells known as hemoglobin, which normally carries oxygen throughout the body.
Inherited Bone Marrow Failure Syndromes
Inherited bone marrow failure syndromes are rare, with fewer than 5,000 people diagnosed worldwide. The genetic mutations associated with these syndromes can affect all the cells in the body – including the different types of blood cells produced in the bone marrow – and the diseases themselves cannot be cured. However, it is possible to treat the blood and marrow complications of these diseases.
Types of inherited bone marrow failure syndromes include:
Typically diagnosed in early childhood, children with Fanconi anemia – the most common type of bone marrow failure syndrome – are unable to produce white blood cells, red blood cells, or platelets. This is typically caused by mutations in one of several genes.
In addition to bone marrow failure, Fanconi anemia can cause abnormal skin pigmentation, abnormal thumbs, smaller eye size, and short stature. Children with this disorder are also at risk for developing leukemia or solid tumors of the head and neck.
Find more information from the Fanconi Anemia Research Fund, Inc.
Dyskeratosis congenita also involves problems with white blood cells, red blood cells, and platelets. Several genes are known to cause Dyskeratosis congenita and can be identified to play a role in over 50 percent of children diagnosed with this disease. In a number of children with this disease, the particular genetic mutation or mutations are unknown. However, a highly sensitive screening test called telomere length analysis is available and can help in making the diagnosis.
Typically diagnosed in adolescents and young adults, this disorder is often associated with clear and dark areas of the skin, nail changes, and white patches in the mouth. Patients are also at risk for developing aplastic anemia. Today we also know that a severe form of this disease can present early in life and must be recognized and diagnosed early so that it can be effectively treated.
Find more information from the Dyskeratosis Congenita Outreach, Inc.
Almost all children with Shwachman-Diamond syndrome have mutations in a gene called SBDS. This blood disorder begins by affecting the production of infection-fighting white blood cells, but progresses to involve problems with red blood cells and platelets as well.
Shwachman-Diamond syndrome is usually diagnosed in early childhood but can be diagnosed as late as when people are in their 40s. The disorder is associated with bone abnormalities and problems with the liver and pancreas, which lead to difficulties with fat absorption in the body.
Find more information from the Shwachman-Diamond Syndrome Foundation.
This bone marrow failure disorder is caused by mutations in genes related to a cell’s ability to produce certain proteins. Children with Diamond-Blackfan anemia make small numbers of red blood cells, while their white blood cell and platelet production is typically normal.
This disorder is usually diagnosed during infancy, and children can have physical abnormalities including abnormal thumbs and short stature, as well as an increased risk of certain types of cancer.
Find more information from the Diamond-Blackfan Anemia Foundation.
Congenital Amegakaryocytic Thrombocytopenia
Congenital amegakaryocytic thrombocytopenia, caused by a mutation involving the MPL gene, affects a child’s blood clot-forming platelets. This disorder can be diagnosed at birth or early in life, due to an infant experiencing poor clotting and easy bruising. This disorder can lead to the failure of red blood cells, white blood cells, and platelets and/or lead to leukemia.
Severe Chronic Neutropenia
Diagnosed in early childhood typically around three years of age, severe chronic neutropenia affects children’s white blood cells, particularly cells called neutrophils. This disorder is related to a mutation in one of more than three genes that affect the production of neutrophils. This syndrome can cause children to develop serious infections during infancy or later in life, including skin infections, mouth ulcers, gum disease, and sinus infections.
Find more information from the Severe Chronic Neutropenia International Registry.
Thrombocytopenia Absent Radii
This inherited blood disorder, usually diagnosed between birth and six months of age, affects a child’s platelets. Children with thrombocytopenia absent radii are missing one of the two bones (known as the radius) from each lower arm, and bruise easily due to the lack of platelets. Mutations in a gene called RBM8A are known to cause this disease.
Acquired Bone Marrow Failure
Acquired bone marrow failure may be of unknown causes (idiopathic) or develop from a variety of situations including exposure to certain chemicals, environmental toxins, viruses, or autoimmune diseases.
Acquired Aplastic Anemia
Acquired aplastic anemia is typically diagnosed in adults, but in rare cases can affect children. It is not inherited through known genes, but can result from exposure to radiation, chemicals, drugs, or viruses. In most children, however, the exact cause is not known.
This disorder involves the bone marrow’s inability to make enough new blood cells of all types – white blood cells, red blood cells, and platelets. These low blood counts can result in a variety of symptoms, which can include fatigue, weakness, dizziness, infections, and excessive bleeding.
The medical condition of children with aplastic anemia can vary dramatically. One day, a child may feel fine, and the next, he or she may experience bruising, bleeding, or fever.
Paraoxysmal Nocturnal Hemoglobinuria
One specific type of acquired aplastic anemia is paroxysmal nocturnal hemoglobinuria (PNH). This results from a gene mutation that is acquired during a person’s lifetime and affects bone marrow or blood stem cells. Children and young adults with PNH may have acquired aplastic anemia, but can also have other complications specific to PNH, including an increased breakdown of red blood cells. When these cells break down, they leak hemoglobin into the blood, which can pass into the urine, giving it a red color.
Find more information from the Aplastic Anemia & MDS International Foundation.
Hemoglobinopathies represent the most common genetic disorders involving the blood. The most common types of hemoglobinopathies – beta-thalassemia and sickle cell disease – affect several million people around the world. These disorders involve genetic defects that have an impact on the production of hemoglobin, a vital protein that delivers oxygen throughout the body.
Types of hemoglobinopathies disorders include:
Beta-thalassemia typically affects people of Mediterranean, Asian, or African descent, and is usually diagnosed within the first year of a child’s life. Children with this disorder are unable to make a protein called globin, a component of hemoglobin. Because of this, these children lack oxygen and red blood cells, which can cause pale skin, fatigue, and weakness and enlargement of organs such as the heart, spleen, and liver.
Find more information from the Cooley’s Anemia Foundation.
Sickle Cell Disease
In sickle cell disease, red blood cells make an abnormal form of beta-globin. This can cause red blood cells to become sickle-shaped, in the form of a crescent. This abnormal shape causes the red blood cells to have problems traveling through blood vessels, so certain tissues in a child’s body do not receive enough blood.
These blood flow problems can happen in the lungs, arms, chest, abdomen, spleen, kidneys, and liver, which can cause pain, stroke, or bacterial infections.
Find more information from the Sickle Cell Disease Association of America.