Methemoglobinemia, beta-globin type

Other Names: Autosomal dominant methemoglobinemia; Hereditary methemoglobinemia due to hemoglobin mutation; M hemoglobinopathy; Hemoglobin M disease; Blue baby syndrome

Methemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. Specifically, it alters a molecule called hemoglobin within these cells. Hemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body.

Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months.

Cause

Methemoglobinemia, beta-globin type is caused by mutations in the HBB gene. This gene provides instructions for making a protein called beta-globin. Beta-globin is one of four components (subunits) that make up hemoglobin. In adults, hemoglobin normally contains two subunits of beta-globin and two subunits of another protein called alpha-globin. Each of these protein subunits is bound to an iron-containing molecule called heme; each heme contains an iron molecule in its center that can bind to one oxygen molecule. For hemoglobin to bind to oxygen, the iron within the heme molecule needs to be in a form called ferrous iron (Fe2+). The iron within the heme can change to another form of iron called ferric iron (Fe3+), which cannot bind oxygen. Hemoglobin that contains ferric iron is known as methemoglobin.

HBB gene mutations that cause methemoglobinemia, beta-globin type change the structure of beta-globin and promote the heme iron to change from ferrous to ferric. The ferric iron cannot bind oxygen and causes cyanosis and the brown appearance of blood.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue.

In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months.

Diagnosis

A baby with this condition will have a bluish skin color (cyanosis) at birth or shortly afterward. The health care provider will perform blood tests to diagnose the condition. Tests may include:

• Checking the oxygen level in the blood (pulse oximetry)
• Blood test to check levels of gases in the blood (arterial blood gas analysis)

Treatment

People with hemoglobin M disease don't have symptoms. So, they may not need treatment. A medicine called methylene blue is used to treat severe MetHb. Methylene blue may be unsafe in people who have or may be at risk for a blood disease called G6PD deficiency. They should not take this medicine. If you or your child has G6PD deficiency, always tell your provider before getting treatment.

Ascorbic acid may also be used to reduce the level of methemoglobin.

Alternative treatments include hyperbaric oxygen therapy, red blood cell transfusion and exchange transfusions.

NIH genetic and rare disease info

• NIH info on Methemoglobinemia, beta-globin type

Methemoglobinemia, beta-globin type is a rare disease.