Hemoglobin H Disease

Introduction:

Hemoglobin H is a type of congenital blood disease that is classified under thalassemia. Thalassemia represents several genetic blood disorders characterized by reduced production of a protein present in red blood cells called hemoglobin. So a decrease in hemoglobin causes a decrease in the count of red blood cells, which leads to a condition called anemia.

Normally, hemoglobin is made up of four protein subunits called two alpha subunits and two beta subunits. Thalassemia is divided into two types, depending on which protein subunit production is impaired. Alpha thalassemia occurs when there is a decrease or absence of production of the alpha subunit. Beta-thalassemia occurs when there is a decrease or absence of beta subunit production.

What Is Hemoglobin H Disease?

Hemoglobin H is a subtype of alpha thalassemia. To produce one alpha subunit, we require two copies of each alpha globin gene, called HBA1 and HBA2. Depending on how many genes are mutated or deleted, there are four types of alpha thalassemias. A moderate-to-severe form of this disease is called hemoglobin H disease in which three alpha globin genes are damaged or deleted out of four genes.

How Is Hemoglobin H Disease Inherited?

This variant of thalassemia is an autosomal recessive genetic disorder. The offspring should receive two copies of defective genes each from the father and mother to be affected by the condition.

What Are the Signs and Symptoms of Hemoglobin H Disease?

The severity of the disease varies from mild to moderate. The symptoms are usually seen in early childhood. Affected individuals have a greater risk of having a child affected by a more severe form of alpha thalassemia called alpha thalassemia major, Hemoglobin Bart syndrome or Hemoglobin Bart’s hydrops fetalis.

• Moderate-To-Severe Anemia (hypochromic microcytic anemia and hemolytic anemia).

• Yellowing of the Eyes and Skin(jaundice).

• Gallstones.

• Frequent infections.

• Lack of energy (fatigue).

• Enlarged spleen (splenomegaly).

• Enlarged liver (hepatomegaly).

• Exercise intolerance.

• Leg ulcers.

• Shortness of breath.

• Lightheadedness.

• Headaches.

• Growth retardation.

• Irritability.

• Changes in bone structure and shape of the head.

• Feeding difficulties.

• Failure to gain weight.

How Is Hemoglobin H Disease Diagnosed?

• Laboratory test:

  • A complete blood count is measured to determine the number, size, shape, maturity, and concentration of red blood cells.

  • Hemoglobin level is usually 7-10 g/dL.

• Hemoglobin Electrophoresis: It is done to identify the different types of hemoglobin present in the blood.

• Peripheral Blood Film: The peripheral blood film is hypochromic and shows microcytosis with inclusion bodies. Inclusion bodies are visualized using a supravital dye such as methyl violet or brilliant cresyl blue.

• Cytology: Bone marrow cytology shows erythroid hyperplasia with inclusion bodies and erythroblasts with less hemoglobin.

• Free-Erythrocyte Protoporphyrin (FEP) And Ferritin Test:

  • These tests are done to rule out iron deficiency anemia by measuring the amount of absorbed iron.

• Genetic Test:

  • DNA analysis is done to evaluate the genetic mutations in HBA1 and HBA2 genes.

  • It provides an accurate diagnosis and prenatal screening for genetic counseling.

  • Genetic testing of other family members can help us find whether an individual is a carrier of a defective gene or not.

• Doppler Ultrasonography: Doppler ultrasonography is used to visualize the developing fetus by using reflected sound waves. It shows the blood flow pattern in the blood vessels of the developing fetus.

• Chorionic Villus Sampling: It is done during the 11th week of pregnancy. A small piece of the placenta is taken for a sample test.

• Amniocentesis: It is used to check the amniotic fluid present around the developing fetus during the 16th week of pregnancy.

How Is Hemoglobin H Disease Treated?

Most of the patients affected by this disease do not require any treatment. However, managing the disease involves the following treatment options.

• Vitamin Supplements: Supplementation of folic acid and any B vitamin might help in red blood cell production. There is a risk of vitamin D or calcium deficiency, so vitamin supplementation is given.

• Avoiding Oxidative Drugs: The affected individuals have the risk of oxidative stress caused by infections, which leads to the premature destruction of red blood cells. This will create a hemolytic crisis, which is an acute and severe anemia and for this reason, oxidative drugs should be contraindicated in these patients.

• Blood Transfusions: Blood transfusions are needed for some individuals to maintain a normal level of healthy hemoglobin in their blood. Repeated transfusions are usually required in early childhood or the late years of adulthood. Blood transfusions are required during any chronic illness, any kind of infection, or when surgery is planned. A plastic tube is inserted intravenously to transfuse blood which takes 1 to 4 hours.

• Iron Chelation: People with severe forms of anemia may need blood transfusions on a regular basis. During regular transfusions, there is an excess amount of iron in the blood called “iron overload”. This iron overload leads to the accumulation of iron in tissues in other parts of the body. To eliminate this excess iron,medications are given called iron chelators. These drugs bind with excess iron and make it dissolve in water. The dissolved iron is excreted through the kidneys. Examples of iron chelators are Deferoxamine,Deferiprone, and Deferasirox.

• Surgical Treatment: Removal of an abnormally enlarged spleen or hyperactive spleen is called a splenectomy. Removal of the spleen has proved to be beneficial. But this surgery carries the risk of blood clot formation in a vein called venous thrombosis. So, the need for surgery is evaluated depending on the severity of the disease.

• Management of Complications: Management of other complications related to other organs is done. For example, for gallstones, surgical removal of the gallbladder is done (cholecystectomy). Any cardiac compaction, which is frequently caused by excess iron accumulation, should be treated as soon as possible.

• Social Support: Genetic counseling and community support are given to patients to overcome their disease and to create social awareness of this common disease.

What Is the Care Given to Pregnant Hemoglobin H Disease Patients?

Pregnant women affected with by condition require high-risk prenatal care since they can have a few complications, such as:

1. Pre-eclampsia or high blood pressure, presence of protein in the urine, change in vision, headache, and sudden weight gain.

2. Antepartum Hemorrhage or excessive bleeding right before delivery.

3. Congestive Heart Failure.

4. Premature Delivery.

5. Miscarriage.

Conclusion:

There is no specific cure for hemoglobin H disease. The symptoms can also be managed symptomatically using an interprofessional approach consisting of primary healthcare providers, hematologists, pediatricians, geneticists, psychologists, and nurses. New advances are being made in treatment for this condition, like hematopoietic stem cell transplantation (HSCT). This procedure involves the elimination of damaged bone marrow cells by chemotherapy or irradiation, and healthy bone marrow from the donor is transplanted, which produces healthy blood cells.