User:Andrewzchang/sandbox/Hemoglobin H Disease

Hemoglobin H Disease (HbH) is a form of alpha thalassemia, or a genetic disorder that reduces the body's ability to produce oxygen-carrying proteins called hemoglobin. Patients who suffer from this disease generally have smaller red blood cells with a less intense red color than usual. Identified by genetic testing, symptoms depend on the variation of the disease. Most patients do not need to receive blood transfusion, but a minority of patients will need frequent blood transfusions as well as other medications. Hemoglobin H is most often found and diagnosed in Africa, the Middle East, India, Southeast Asia, and the Mediterranean region and is most seen in areas with warm climates and high malaria cases. It is thought that alpha thalassemia traits are protective against malaria.

Screening and Diagnosis
Newborns are typically screened for Hemoglobin H in the United States, but adults can also have their DNA tested to detect the disease. Patients diagnosed with Hemoglobin H should undergo further testing to determine if they have a variant of the disease.

Symptoms
Symptoms for Hemoglobin H can vary a lot depending on the patient and the variation of the disease. Some patients are asymptomatic for their entire life, while others may suffer from episodic anemia and require frequent blood transfusions. Patients of Hemoglobin H are often referred to hematologists, or blood specialists who can correctly diagnose the disease and give the correct evaluation of treatments. Furthermore, family members of patients diagnosed with Hemoglobin H are also recommended to have genetic testing.

Risk for Children and Pregnancies
Most newborns and young children are not affected by HbH and are asymptomatic, but a few children and fetuses who inherited a harsher variation of the disease often suffer more severe symptoms. Some of the symptoms include underdevelopment in growth, an increased risk of anemia for the mother and the fetus, or HbH hydrops fetalis syndrome- a variation of HbH that puts fetuses in extreme risk for anemia and hypoxia, or a lack of oxygen carried to tissue to maintain homeostasis, which can lead to swelling, buildup of fluid in the heart, structural abnormalities, and even death. The cause of this variation is not well understood.

Treatments and Management
Some treatments for Hemoglobin H Disease include:

● Folic acid supplements (0.5g-1g a day)- which help red blood cell production

● Blood count monitoring- frequently getting tested for blood levels

● Blood transfusions when necessary

● Iron chelation support (helps limit excess iron in the blood)

● In extreme cases, Splenectomy is recommended, but often only to patients that have multiple episodes of a sudden fall in hemoglobin levels(7)

Patients with Hemoglobin H Disease need to be monitored closely for oxidant stress, typically caused by illness or oxidant drug use. It is recommended for adults with HbH to get genetic counseling and for his or her partner to be tested to determine if there is any risk for the fetus for contracting the disease.

Causes of the Disease
Similar to other types of Alpha Thalassemia, there is an imbalance of globin chains needed to create hemoglobin. Located on the 16th chromosome, there are 3 different types of hemoglobin: hemoglobin A, hemoglobin A2, and hemoglobin F, which are made up of different combinations of alpha, beta, gamma, or delta globin molecules. In Hemoglobin H disease, three out of the four genes needed to produce alpha globin chains are either nonexistent, inactive, or mutated, resulting in a deficiency in the production of alpha globin chains. Hemoglobin A, or 95%-98% of a normal adult's hemoglobin is made up of one pair of alpha-beta globin chains. Patients with HbH do not produce enough alpha globin chains to combine with beta globin chains to create normal levels of hemoglobin A, leading to excess beta globin chains and a deficiency of normal hemoglobin (hemoglobin A). The excess beta globin chains then combine with each other to create Hemoglobin H, the origin of the name of this disease.

Variation between Patients
Depending on the mutation type and variation of Hemoglobin H Disease a patient suffers from, symptoms have variable effects on the body.

Deleted genes
In the majority of Hemoglobin H patients, both alpha globin genes are deleted in one chromosome 16 plus only one deletion in the other chromosome 16. This is known as deletion Hemoglobin H and is much more mild than the other variations. Patients are often asymptomatic through infancy and early childhood and their symptoms as adults are less severe.

Non-deleted genes
In some rare cases, patients will have both alpha globin genes deleted in one chromosome 16, while the other chromosome has a point mutation, or an insertion/deletion, involving an alpha globin gene in the other chromosome. This is called a nondeletional Hemoglobin H and patients with this variation typically have more severe symptoms. This is suspected to be caused by unstable alpha globin chains or variant hemoglobin being created. Patients with nondeletional HbH are more prone to symptoms such as :

● Splenomegaly- enlarged spleen

● Hepatomegaly- enlarged liver

● Cholelithiasis- the presence of gallstones in the gallbladder

● Limited growth

● A decreased bone density

● More blood transfusions needed

● Higher concentration of Hemoglobin H (beta-beta combination instead of an alpha-beta combination)

Patients with deletion Hemoglobin H can still suffer from these symptoms, but the symptoms are often much less severe and common.

Biology Behind the Disease
Considered a moderate to severe Alpha Thalassemia, HbH can cause hypochromia, or when red blood cells have less color than they typically do, and microcytosis, where red blood cells are smaller than usual.

Effects on Red Blood Cells
Hemoglobin H is also very unstable and can oxide easily to create precipitate inside red blood cells. This precipitate can cause early cell death because it often attaches to the cell membrane which leads to local oxidative damage, membrane dysfunction, and rigidity of the cell membrane.

Effects of Other Diseases
With fever, patients are known to have a rapid increase of HbH bodies in their red blood cells. This can lead to a hemolytic crisis, or when more red blood cells are destroyed than created, leading to a dangerous drop in hemoglobin.

Iron Overload
Hemoglobin H. typically causes an iron overload in red blood cells because it increases iron absorption. Iron overload can lead to many symptoms, including hemosiderosis (an increase of iron deposits inside tissue, often in the lungs or kidneys), diabetes, and in severe cases, heart failure from iron overload.