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What

Methemoglobinemia is a condition in which hemoglobin (the molecule in blood that carries oxygen) is defective and cannot carry oxygen. Iron molecules are normally present in hemoglobin in the chemically “reduced” state. Only in this state can they carry oxygen. In methemoglobinemia, the heme iron is in the “oxidized” state in which it is chemically impossible for it to carry oxygen. Furthermore, reduced molecules prevent normally oxidized molecules from delivering oxygen normally. The defective hemoglobin is called methemoglobin (metHb). The lack of oxygen in the tissues of the body can result in cyanosis (bluish skin color). Methemoglobinemia may be hereditary or acquired (brought on by exposure to certain chemicals- see below). There are two general types of hereditary methemoglobinemia: hemoglobin M disease (Type I) and methemoglobin-reducing enzyme deficiency (Type II). However, acquired methemoglobinemia is the most common cause of this condition.

Who

congenital methemoglobinemia is a rare disease; the acquired form is more common in developing nations and rural areas of developed nations where water is contaminated with chemicals that cause the condition.

Signs and Symptoms

A person with methemoglobinemia may have the following symptoms: Type I Bluish tint of the skin Type II- the same symptoms as type I plus: Mental retardation Delayed or slow development Poor growth and weight gain Acquired- the same symptom as type I plus: Headache Fatigue Shortness of breath Lack of energy Seizures Death Symptoms can range from mild to life threatening. The severity of the disease increases as the proportion of metHb in the blood increases. For example, if the amount of metHb in the blood is less than 10% there are often no symptoms, if greater than 15% the person is in danger of cerebral ischemia (lack of oxygen to the brain), if greater than 60% death can occur. Between 10-60% other symptoms vary. The amount of metHb in the body is normally less than 2% of total hemoglobin.

Possible Causes

One hereditary cause of methemoglobinemia is a deficiency in an enzyme (such as NADH metHb reductase or cytochrome b5 reductase) that helps the body to return methemoglobin to normal hemoglobin by reducing (‘un-oxidizing’) heme iron. This type of methemogobinemia is inherited in an autosomal recessive pattern, meaning that a child must receive an abnormal gene from both parents to have the condition. In this case, the abnormal gene cannot tell the body how to make one of the heme iron-reducing enzymes resulting in an abnormally low amount of the enzyme and thus a buildup of metHb. Another type of inherited methemoglobinemia is called hemoglobin M (HbM) disease. There are several forms of this condition. All forms of HbM disease are caused by a mistake in a gene that causes the body to produce an irregular type of hemoglobin called hemoglobin M. In hemoglobin M disease there is an abnormal interaction between the hemoglobin and heme iron such that iron is kept in the oxidized form and metHb builds up. The gene(s) responsible for HbM disease are inherited in an autosomal dominant pattern, meaning that if a child receives a single abnormal hemoglobin gene from one affected parent and a normal hemoglobin gene from the other parent, the child will be born with this condition. Acquired methemoglobinemia is caused by exposure (ingestion or skin contact) to chemicals that oxidize the iron in hemoglobin. A list of these chemicals can be found in table 2 of the eMedicine reference below.

Diagnosis

Methemoglobinemia should be suspected if: 1. There is cyanosis with a normal amount of oxygen in the blood 2. There is an abnormally high amount of metHb in the blood 3. There is an abnormal optical spectrum (pattern of light absorbance) of hemoglobin 4. There is a low level of one of the reducing-reducing enzymes 5. There has been exposure to one or more of the chemicals that trigger methemoglobinemia 6. There is a brown color to blood in the presence of previously mentioned symptoms.

Treatment

Severe methemoglobinemia can be treated by giving the child a dose of a medication called methylene blue, which helps the methemoglobin-reducing enzymes work more efficiently. Ascorbic acid is used to treat hemoglobin M and specific enzyme deficiencies. If chemical exposure is suspected, the condition is treated by avoiding the chemical. A blood transfusion may be given during a life-threatening episode to quickly replace the metHb with normal hemoglobin.

Prognosis

Hereditary methemoglobinemia is usually mild with few or no complications throughout life. With both congenital and acquired methemoglobinemia the course and outcome of the condition depends on overall health, and levels of metHb in the blood.

Connect with other parents

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Weblinks

Medline Plus
Well written information for patients and families.

Genetics Home Reference
A good source of information on the genetics of methemoglobinemia for patients and families.

Google Search for Methemoglobinemia

References and Sources

www.nlm.nih.gov/medlineplus/ency/article/000562.htm www.1uphealth.com/health/methemoglobinemia_info.html ghr.nlm.nih.gov/ghr/disease/methemoglobinemiabetaglobintype www.emedicine.com/med/topic1466.htm harrisons.accessmedicine.com/server-java/Arknoid/amed/harrisons/co_chapters/ch106/ch106_p13.html