National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Anemia, Megaloblastic is not the name you expected.
Megaloblastic anemia is a condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts). Bone marrow, the soft spongy material found inside certain bones, produces the main blood cells of the body -red cells, white cells, and platelets. Anemia is a condition characterized by the low levels of circulating, red blood cells. Red blood cells are released from the marrow into the bloodstream where they travel throughout the body delivering oxygen to tissue. A deficiency in healthy, fully-matured red blood cells can result in fatigue, paleness of the skin (pallor), lightheadedness and additional findings. Megaloblastic anemia has several different causes - deficiencies of either cobalamin (vitamin B12) or folate (vitamin B9) are the two most common causes. These vitamins play an essential role in the production of red blood cells.
In most cases, megaloblastic anemia develops slowly and affected individuals may remain without any apparent symptoms (asymptomatic) for many years. Symptoms common to anemia usually develop at some point and may include fatigue, paleness of the skin (pallor), shortness of breath, lightheadedness, dizziness and a fast or irregular heartbeat. The specific symptoms present in each individual can vary greatly.
Additional common symptoms include aches and pains, muscle weakness, and difficulty breathing (dyspnea). Individuals with megaloblastic anemia may also develop gastrointestinal abnormalities including diarrhea, nausea, and loss of appetite. Some affected individuals may develop a sore, reddened tongue. These abnormalities may result in unintended weight loss. Mild enlargement of the liver (hepatomegaly) and a slight yellowing of the skin or eyes (jaundice) may also occur.
Megaloblastic anemia resulting from cobalamin deficiency may also be associated with neurological symptoms. The initial neurological symptom may be tingling or numbness in the hands or feet. Additional symptoms develop over time including balance or gait problems, vision loss due to degeneration (atrophy) of the nerve that transmits impulses from the retina to the brain (optic nerve), and mental confusion or memory loss. A variety of psychiatric abnormalities have also been reported in individuals with cobalamin deficiency including depression, insomnia, listlessness, and panic attacks. The spectrum of potential neuropsychological symptoms potentially associated with cobalamin deficiency is large and varied.
In rare cases of cobalamin deficiency, neurological symptoms may occur before the characteristic findings of anemia. Folate deficiency is generally considered not to result in neurological symptoms, although some recent research suggests that, in rare cases, it may cause some neurological symptoms.
The most common causes of megaloblastic anemia are deficiency of either cobalamin (vitamin B12) or folate (vitamin B9). These two vitamins serve as building blocks and are essential for the production of healthy cells such as the precursors to red blood cells. Without these essential vitamins, the creation (synthesis) of deoxyribonucleic acid (DNA), the genetic material found in all cells, is hampered.
Vitamin deficiency resulting in megaloblastic anemia may result from inadequate intake of cobalamin and folate in the diet, poor absorption of these vitamins by the intestines or improper utilization of these vitamins by the body. Folate deficiency may also result from conditions which use up or require excessive amounts of folate.
Cobalamin is found in meat, fish and eggs. Deficiency of cobalamin due to poor dietary intake is extremely rare, but has occurred in some total vegetarians (vegans). The most common cause of cobalamin deficiency is impaired absorption of the vitamin by the small intestines (malabsorption). In such cases, the body contains enough of the vitamin, but cannot absorb and subsequently use the vitamin. Malabsorption may result from surgery on the intestines, intestinal diseases such as Crohn's disease or tropical sprue, or infection (bacterial growth) within the gastrointestinal tract. Pernicious anemia may also cause cobalamin deficiency. This form of anemia is characterized by a lack of intrinsic factor, a protein that binds with cobalamin and aids in its absorption by the small intestines. Without enough intrinsic factor, the body cannot absorb enough cobalamin.
In rare cases, a fish tapeworm known as Diphyllobothrium latum may take root in the small intestine and use up cobalamin, thereby depriving the body of necessary amounts of this essential vitamin. In some cases, bacteria may compete with the body for cobalamin as in blind loop syndrome, a disorder in which obstruction of the small intestines results in the abnormal build up of bacteria in the gastrointestinal tract.
Folate, which is also known as folic acid, is a B vitamin that is normally found in green leafy vegetables, citrus fruits, and certain grains and nuts. Folate deficiency can occur in diets that supply insufficient amounts of these foods. Alcoholics may develop folate deficiency because alcohol does not contain folate and may impair the breakdown (metabolism) of folate in the body. Surgery involving the stomach or intestines can result in impaired absorption of folate. Certain intestinal disorders such as Crohn's disease or tropical sprue can cause malabsorption and subsequent folate deficiency.
Pregnant women, women who are breastfeeding, individuals who have chronic hemolytic anemias, and individuals undergoing hemodialysis for kidney disease all have higher-than-normal demands for folate. Failure to adequately supplement folate in these individuals can potentially result in folate deficiency.
Certain medications can impair the body's ability to absorb folate including many drugs used to treat cancer. Medications can also impair the synthesis of DNA resulting in megaloblastic anemia.
Much rarer causes of megaloblastic anemia (unrelated to vitamin deficiency) have been identified including rare enzyme deficiencies known as inborn errors of metabolism and primary bone marrow disorders including myelodysplastic syndromes and acute myeloid leukemia.
In some cases, the cause of megaloblastic anemia is unknown (idiopathic).
Megaloblastic anemia affects males and females in equal numbers. It can occur in individuals of any racial or ethnic background. Because the causes of megaloblastic anemia vary and because some individuals may not exhibit any obvious symptoms (asymptomatic), determining its true frequency in the general population is difficult.
Symptoms of the following disorders can be similar to those of megaloblastic anemia. Comparisons may be useful for a differential diagnosis.
Pernicious anemia is a rare blood disorder characterized by the inability of the body to properly utilize vitamin B12, which is essential for the development of red blood cells. Most cases result from the lack of the gastric protein known as intrinsic factor, without which vitamin B12 cannot be absorbed. The symptoms of pernicious anemia may include weakness, fatigue, an upset stomach, an abnormally rapid heartbeat (tachycardia), and/or chest pains. Recurring episodes of anemia (megaloblastic) and an abnormal yellow coloration of the skin (jaundice) are also common. Pernicious anemia is thought to be an autoimmune disorder, and certain people may have a genetic predisposition to this disorder. There is a rare congenital form of pernicious anemia in which babies are born lacking the ability to produce effective intrinsic factor. There is also a juvenile form of the disease, but pernicious anemia typically does not appear before the age of 30. The onset of the disease is slow and may span decades. When the disease goes undiagnosed and untreated for a long period of time, it may lead to neurological complications. Nerve cells and blood cells need vitamin B12 to function properly.
(For more information on this disorder, choose "pernicious anemia" as your search term in the Rare Disease Database.)
In some cases, the structural changes in the abnormal red cells (megaloblasts) that characterized megaloblastic anemia have been mistaken for certain primary bone marrow disorders such as acute myeloid leukemia, myelodysplastic syndromes and aplastic anemia. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
A diagnosis of megaloblastic anemia is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of blood tests. Blood tests may reveal the abnormally large, misshapen red blood cells that characterize megaloblastic anemia. Blood tests can also confirm cobalamin or folate deficiency as the cause of megaloblastic anemia. Additional tests such as a Schilling test, which confirms poor absorption as the cause of cobalamin deficiency, may be necessary.
The treatment of megaloblastic anemia depends upon the underlying cause of the disorder. Dietary insufficiency of cobalamin and folate can be treated with appropriate changes to the diet and the administration of supplements. In individuals who cannot absorb cobalamin or folate properly, life-long supplemental administration of these vitamins may be necessary. Prompt treatment of cobalamin deficiency is important because of the risk of neurological symptoms.
If underlying disorders (e.g., Crohn's disease, tropical sprue, celiac sprue, blind loop syndrome, inborn errors of metabolism) are the cause of these vitamin deficiencies, appropriate treatment for the specific disorder is required. Supplementation of either cobalamin or folate may also be required.
If medications are the cause of vitamin deficiency then use of the medication in question should be stopped or the dosage lowered.
Preventive (prophylactic) folate supplementation may be recommended for individuals who have higher-than-normal demands for folate such as pregnant women.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:898-899, 990-991.
Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison's Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:601-607.
Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:843-851.
Aslinia, F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res. 2006;4:236-241.
De Paz R, Hernandez-Navarro F. Management, prevention and control of megaloblastic anemia, secondary to folic acid deficiency. Nutr Hosp. 2006;113-119.
Ward PC. Modern approaches to the investigation of vitamin B12 deficiency. Clin Lab Med. 2002;22:435-45.
Reynolds EH. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry. 2002;72:567-71.
Neufeld EJ, Fleming JC, Tartaglini E, et al. Thiamine responsive megaloblastic anemia syndrome: a disorder of high-affinity thiamine transport. Blood Cells Mol Dis. 2001;27:135-38.
Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999;36:19-34.
Wickramasinghe SN. The wide spectrum and unresolved issues of megaloblastic anemia. Semin Hematol. 1999;36:3-18.
FROM THE INTERNET
Schick P. Davis TH. Megaloblastic Anemia. Emedicine Journal, January 29, 2007.
Available at: //www.emedicine.com/MED/topic1420.htm
Accessed on: February 12, 2008.
Harper JL, Sarnaik S. Megaloblastic Anemia. Emedicine Journal, August 20, 2007.
Available at: //www.emedicine.com/ped/topic2575.htm
Accessed on: February 12, 2008
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:190450; Last Update:03/17/2004. Available at: //www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190450 Accessed on: April 6, 2007.
Mayo Clinic for Medical Education and Research. Vitamin Deficiency Anemia. March 9, 2007.
Available at: //www.emedicine.com/ped/topic2575.htm
Accessed On: February 12, 2008.
Genetic and Rare Diseases (GARD) Information Center
- PO Box 8126
- Gaithersburg, MD 20898-8126
- Tel: (301)251-4925
- Fax: (301)251-4911
- Tel: (888)205-2311
- Website: //rarediseases.info.nih.gov/GARD/
NIH/National Heart, Lung and Blood Institute
- P.O. Box 30105
- Bethesda, MD 20892-0105
- Tel: (301)592-8573
- Fax: (301)251-1223
- Email: firstname.lastname@example.org
- Website: //www.nhlbi.nih.gov/
For a Complete Report
This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.
For additional information and assistance about rare disorders, please visit the National Organization for Rare Disorders web site at www.rarediseases.org
The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only.
It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report.
This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.
Last Updated: 2/25/2008
Copyright 2008 National Organization for Rare Disorders, Inc.
Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.