Not all patients with megaloblastic anemia are symptomatic [5]. Patients with megaloblastosis may present with a history of the following features:

• Abdominal discomfort or bloating
• Anemia
• Anorexia
• Nausea
• Pale yellow skin 
• Sore tongue
• Weakness
• Lethargy
• Weight loss
• Constipation
• Bleeding per rectum may be suggestive of inflammatory bowel disease like Crohn disease
• Canker sores
• Consumption of raw fish may have led to infestation of tapeworm.
• Mental status changes (psychosis)
• Neurological deficits (paresthesia, numbness, pain, tingling, burning sensation, unsteady gait, loss of balance)
• Patients with other autoimmune disorders like type 1 diabetes or Graves disease should be suspected of having pernicious anemia.
• Prior abdominal surgery such as gastrectomy. A history of bowel resection may suggest blind loop syndrome.
• Strict vegetarian diet with no intake of dairy products or eggs.

Physical examination

• Tachycardia
• Dyspnea
• Tachypnea
• Yellowish skin discoloration (due to the anemia and jaundice) 
• Atrophic glossitis
• Neuropsychiatry evaluation may reveal paresthesias, numbness, weakness, loss of dexterity, impaired memory, and peripheral neuropathy 
• Loss of balance, abnormal gait, loss of proprioceptive senses, speech impairment, and absent vibratory senses may be caused by subacute combined degeneration of the cord due to vitamin B12 deficiency.
• Visual exam may reveal diminished or complete loss of vision due to optic atrophy
• Malabsorption features may include profuse diarrhea, abdominal distension, and steatorrhea

• Anemia

  Furthermore bone marrow examination supported the diagnosis of megaloblastic anemia. [omicsonline.org]

  D51.3 Other dietary vitamin B12 deficiency anemia D51.8 Other vitamin B12 deficiency anemias D51.9 Vitamin B12 deficiency anemia, unspecified D52 Folate deficiency anemia D52.0 Dietary folate deficiency anemia D52.1 Drug-induced folate deficiency anemia [icd10data.com]

  In FA 2007 it says that Phenytoin causes a megaloblastic anemia due to decreased folate absorption. [forums.studentdoctor.net]

  See also: Anemia - B12 deficiency Folate-deficiency anemia Pernicious anemia Symptoms See: Anemia - B12 deficiency Folate-deficiency anemia Pernicious anemia Exams and Tests For testing information, see: Anemia - B12 deficiency Folate-deficiency anemia [web.archive.org]

• Fatigue

  The most frequent symptoms were fatigue and mild abdominal pain, which were identified in approximately 66.6% of the 18 patients interviewed. Fourteen patients received treatment with niclosamide and all were cured. [ncbi.nlm.nih.gov]

  Symptoms include chronic anemia, fatigue, yellow skin and eyes (jaundice), pale skin, and missing fingers and toes at birth. Some people never need treatment. [webmd.com]

  Some people have problems in absorbing vitamin B12 which is the reason that produces them meglobastic anemia Between the main symptoms of the anemia we have: Continued Fatigue. Fatigue with little effort. Problems in the breathing. [botanical-online.com]

  The main symptoms of pernicious anemia are tiredness, shortness of breath and fatigue. Fatigue is often the first sign of folic acid deficiency anemia. [diagnose-me.com]

• Pallor

  Abstract A nine years old boy presented with history of pallor and anaemia since early infancy along with neural hearing loss responding to empirical multivitamin and folic acid therapy started on basis of blood complete picture showing anaemia and megaloblastic [ncbi.nlm.nih.gov]

  Abstract Megaloblastic bone marrow transformation was observed in a 7 years old girl, showing pallor since age 2. [nature.com]

  Author: Volodymyr Shponka, MD; Maria Proytcheva, MD Category: Red Cell: Other Disorders > Megaloblastic Anemia > B12 / folate Published Date: 07/11/2017 An 8-month-old female, exclusively breastfed, presented with pallor and a two-month history of vomiting [imagebank.hematology.org]

• Anorexia

  He complained about anorexia and frequent epistaxis in the last week too. [ejinme.com]

  Weight loss and lack of appetite ( anorexia ) may also occur, as well as jaundice, confusion and depression. Lesions in the gastrointestinal tract may cause abnormal activity in the intestines and difficulties with the absorption of food. [diagnose-me.com]

  […] anemia Most common cause of vitamin B12 deficiency Absence of IF Autoimmune destruction of parietal cell antibodies (PCA) is most common etiology 80% have PCA; ≥50% have IF-blocking antibodies Clinical Presentation Often present with anemia Pale skin Anorexia [arupconsult.com]

• Difficulty Walking

  Common symptoms include: Pale skin Irritability Poor appetite Smooth and painful tongue Stomach problems Numbness/tingling in hands and feet Difficulty walking Muscle weakness Fatigue Fast/irregular heartbeat Trouble breathing and Lightheadedness or dizziness [nicklauschildrens.org]

  Symptoms may include: Abnormal paleness or lack of color of the skin Decreased appetite Irritability Lack of energy or tiring easily (fatigue) Diarrhea Difficulty walking Numbness or tingling in hands and feet Smooth and tender tongue Weak muscles The [lpch.org]

  Some of the most common symptoms of megaloblastic anemia include: Abnormal paleness or lack of color of the skin Decreased appetite Irritability Lack of energy or tiring easily (fatigue) Diarrhea Difficulty walking Numbness or tingling in hands and feet [chop.edu]

• Dyspnea

  She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. [ncbi.nlm.nih.gov]

  […] given appointment for follow up. 3 weeks later, the patient had no chest pain, even without pain killers, and had no dyspnea. [esciencecentral.org]

  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. [rarediseases.org]

• Respiratory Distress

  At physical examination, the patient was awake and oriented; his vital signs were temperature 37 °C, blood pressure 85/44 mm Hg, heart rate 115 bpm, and respiratory rate 24/min, without signs of respiratory distress. [ejinme.com]

  Respiratory distress may be due to pleural involvement. [emdocs.net]

  distress was urgently transported to our hospital. [dovepress.com]

  Adult respiratory distress syndrome. Respiratory failure leading to death. Pericarditis. Secondary pneumonia. Pleural effusions and empyema. Pneumomediastinum, pneumoperitoneum and pneumothorax. [patient.info]

  This is followed by </li></ul><ul><li>a fulminant phase of acute mediastinitis, with respiratory distress, chest pain, cyanosis, and prostration. [slideshare.net]

• Loss of Appetite

  Inclusion criteria for the study were; age 9 to 36 months, refusal of food except for breast and cow milk, loss of appetite, developmental delay, significant pallor, and hypersegmentation neutrophils in the peripheral blood smear. [ncbi.nlm.nih.gov]

  Symptoms of Megaloblastic Anaemia  shortness of breath  muscle weakness  abnormal paleness of the skin  glossitis (swollen tongue)  loss of appetite/weight loss  diarrhea  nausea  fast heartbeat  smooth or tender tongue  tingling in hands and [slideshare.net]

  Loss of appetite Pale and haggard appearance Sensation of lack of sanguineous circulation in the fingers and feet. Diarrhoea. Headache Lack of concentration or memory loss. etc. [botanical-online.com]

  Symptoms include diarrhea or constipation; fatigue, lack of energy, or light-headedness when standing up or with exertion; loss of appetite; pale skin; problems concentrating, mostly during exercise; swollen, red tongue or bleeding gums. [childrensmn.org]

  If symptoms are present, they may include: Pale skin Crankiness Weakness Fatigue Neurologic problems including trouble with balance, coordination, or memory Digestive problems including nausea, vomiting, constipation, diarrhea, or loss of appetite How [sterlingcare.com]

• Constipation

  Symptoms include diarrhea or constipation; fatigue, lack of energy, or light-headedness when standing up or with exertion; loss of appetite; pale skin; problems concentrating, mostly during exercise; swollen, red tongue or bleeding gums. [childrensmn.org]

  If symptoms are present, they may include: Pale skin Crankiness Weakness Fatigue Neurologic problems including trouble with balance, coordination, or memory Digestive problems including nausea, vomiting, constipation, diarrhea, or loss of appetite How [sterlingcare.com]

  CASE REPORT A 22-year-old woman had been referred to our pediatric outpatient clinic with the complaints of pale skin, loss of appetite, ataxia and diarrhea-constipation periods when she was 2-year-old. [revistanefrologia.com]

  These are some of the symptoms of megaloblastic anemia: Pale or yellow skin Fast heart beat Shortness of breath Lack of energy, feeling tired Decreased appetite Irritability or fussiness Hair color changes Stomach upsets, nausea, diarrhea, gas, constipation [stanfordchildrens.org]

• Failure to Thrive

  The mothers are usually not anemic, and failure to thrive and neurologic deficits are more common in their infants than in megaloblastic anemia. [ncbi.nlm.nih.gov]

  Similar to our patient, Wulffraat et al. [6] reported two girls with definite diagnosis of IGS, who their first manifestation was a failure to thrive. [indianjnephrol.org]

  Clinical description Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of the patients. [orpha.net]

  Clinical features include megaloblastic anemia, recurrent infections, failure to thrive, and proteinuria. Recessive mutations in cubilin (CUBN) and in amnionless (AMN) have been shown to cause IGS. [academic.oup.com]

• Headache

  Headache Lack of concentration or memory loss. etc. Causes of megaloblastic anemia The main causes that produce this type of anemia are: - Lack of B12 vitamin. [botanical-online.com]

  Symptoms for both types include: Chest pain Fast heartbeat, or tachycardia Headaches Trouble breathing Weakness and fatigue Treatment for sideroblastic anemia depends on the cause. [webmd.com]

  The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and feet. [ghr.nlm.nih.gov]

• Numbness of the Hand

  Common symptoms include: Pale skin Irritability Poor appetite Smooth and painful tongue Stomach problems Numbness/tingling in hands and feet Difficulty walking Muscle weakness Fatigue Fast/irregular heartbeat Trouble breathing and Lightheadedness or dizziness [nicklauschildrens.org]

  The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, diarrhea, and tingling or numbness in the hands and feet. [ghr.nlm.nih.gov]

  The initial neurological symptom may be tingling or numbness in the hands or feet. [rarediseases.org]

• Abnormal Gait

  Neurological symptoms may include muscular weakness and abnormal gait. Etiology Patients have bi-allelic mutations in the GIF gene on chromosome 11 encoding the gastric Intrinsic Factor (IF), a protein necessary for the absorption of vitamin B12. [orpha.net]

  Megaloblastic anemia is a hematological disorder that characterized by abnormally large cells that have arrested in nuclear maturation. [symptoma.com]

  […] pigmentation of hair A broad spectrum of mental changes: from irritability to psychosis Peripheral neuropathy: seen in both folate and cobalamin deficiencies Subacute combined degeneration: abnormal gait, loss of balance, speech impairment and loss of [pathologyoutlines.com]

  Peripheral neuropathy, abnormal gait, loss of balance, loss of proprioception and vibratory senses, blindness due to optic atrophy, depression, loss of memory, and psychiatric disorders may occur. [sites.google.com]

• Clumsiness

  Feelings of numbness, tingling, weakness, lack of coordination, clumsiness, impaired memory, and personality changes can all occur. Both sides of the body are usually affected, and the legs are typically more affected than the arms. [medicinenet.com]

• Giddiness

  This form of megaloblastic anaemia will share symptoms of other types of anaemia, such as: tiredness lack of energy insomnia feeling faint/giddy breathlessness, particularly on exertion. [nutritionist-resource.org.uk]

Patients with suspected megaloblastic anemia usually require a comprehensive workup that includes the following [6]:

• Blood smear usually shows macroovalocytes having an MCV >115 fl, anisocytosis, poikilocytosis, hypersegmented neutrophils, Howell-Jolly bodies and nucleated RBCs.
• Complete blood count that includes reticulocyte count, serum chemistry, lactate dehydrogenase (LDH) levels, indirect and direct bilirubin levels, levels of iron, ferritin, folate and cobalamin. Blood should usually be drawn prior to a meal or transfusion to avoid falsely elevated levels.
• Bone marrow aspiration is done to rule out a primary bone marrow disorder such as a myelodysplastic syndrome or leukemia and assess iron stores. 
• Levels of methylmalonic and homocysteine can differentiate between folate and cobalamin deficiency. Levels of both metabolites are increased in patients with cobalamin deficiency but in folate deficiency only homocysteine is elevated [7] [8].
• Patients with defects or absence of intrinsic factor need to undergo the Schilling test, when this test is available.
• Patients in whom the testing has been non-conclusive will need an empirical trial of folate and cobalamin. It is important not to give folate only in the presence of suspected cobalamin deficiency as this can worsen the neurological deficit.
• If a blind loop syndrome is suspected, imaging with barium swallow and follow-through series of the gastrointestinal tract is necessary. 
• If the above tests are not productive one may need to rule out autoimmune disorders, pancreatic insufficiency, tapeworm infestation, Crohn disease or Zollinger Ellison syndrome. Patients with folate deficiency may need to be worked up for malnutrition, celiac disease, alcoholism, exfoliative dermatitis and chronic hemolysis.

• Macrocytic Anemia

  After 1 year, macrocytic anemia developed and the thiamine therapy was started at 75 mg/day. During the follow-up, the insulin requirement decreased and even ceased, and macrocytic anemia improved with thiamine treatment. [ncbi.nlm.nih.gov]

  […] megaloblastic anemia 1 IGS megaloblastic anaemia edit English megaloblastic anemia macrocytic anemia that is characterized by inhibition of DNA synthesis during red blood cell production Grasbeck-Imerslund syndrome Imerslund-Grasbeck syndrome MGA1 Norwegian [wikidata.org]

  TOC | HEME Approach to Macrocytic /Megaloblastic Anemia By means of morphologic and biochemical criteria, macrocytic anemias can be divided into two groups: The megaloblastic anemias ( the presence of hypersegmented neutrophils and oval macrocytes in [enotes.tripod.com]

  For example, while alcoholism alone may cause nonmegaloblastic macrocytic anemia, people who abuse alcohol are often folate-deficient, as well, which could trigger a megaloblastic macrocytic anemia. [livehealthy.chron.com]

• Macrocytosis

  Sunitinib, a multitargeted tyrosine kinase inhibitor can also incite macrocytosis and consequent anemia. An association between sunitinib-based treatment and macrocytosis was established earlier. [omicsonline.org]

  Nonmegaloblastic macrocytosis occurs in various clinical states, not all of which are understood. Anemia commonly occurs in patients with macrocytosis but usually results from mechanisms independent of macrocytosis. [merckmanuals.com]

  Nonmegaloblastic macrocytosis occurs in various clinical states, not all of which are understood. Anemia can occur in patients with macrocytosis due to mechanisms independent of the macrocytosis. [msdmanuals.com]

  Keep in mind guys that the liver stores B12 and you can go years before you see any macrocytosis. [forums.studentdoctor.net]

• Anisocytosis

  In five of the eight episodes, erythropoiesis was not megaloblastic and there was insufficient anisocytosis or poikilocytosis to suggest an underlying vitamin deficiency state. [jamanetwork.com]

  Diagnosis is usually based on a CBC and peripheral smear, which usually shows a macrocytic anemia with anisocytosis and poikilocytosis, large oval RBCs (macro-ovalocytes), hypersegmented neutrophils, and reticulocytopenia. [merckmanuals.com]

  The smear shows macro-ovalocytosis, anisocytosis (variation in RBC size), and poikilocytosis (variation in RBC shape). The RDW is high. Howell-Jolly bodies are common. Reticulocytopenia is present. [msdmanuals.com]

  Clinical signs macrocytic normochromic anemia pernicious anemia: also atrophic glossitis, atrophic gastritis, neurologic disorders Histology Peripheral blood: normochromic macrocytic anemia, often pancytopenia, significant anisocytosis, poikilocytosis [atlases.muni.cz]

• Poikilocytosis

  In five of the eight episodes, erythropoiesis was not megaloblastic and there was insufficient anisocytosis or poikilocytosis to suggest an underlying vitamin deficiency state. [jamanetwork.com]

  Diagnosis is usually based on a CBC and peripheral smear, which usually shows a macrocytic anemia with anisocytosis and poikilocytosis, large oval RBCs (macro-ovalocytes), hypersegmented neutrophils, and reticulocytopenia. [merckmanuals.com]

  The smear shows macro-ovalocytosis, anisocytosis (variation in RBC size), and poikilocytosis (variation in RBC shape). The RDW is high. Howell-Jolly bodies are common. Reticulocytopenia is present. [msdmanuals.com]

  On the laboratory examination peripheral blood smears disclosed macrocytic anemia with moderate poikilocytosis. Moderate leukopenia with shift to left change and many hypersegmented neutrophils were found. [annlabmed.org]

• Howell-Jolly Bodies

  Although iron deficiency can mask macrocytosis, Howell-Jolly bodies and granulocyte hypersegmentation should still be present. Serum B12 and folate levels should be measured. [msdmanuals.com]

  bodies, nuclei-containing erythrocytes, basophilic stippling. [atlases.muni.cz]

  Howell-Jolly bodies (residual fragments of the nucleus) are common. Reticulocytopenia is present. Hypersegmentation of the granulocytes develops early; neutropenia develops later. [merckmanuals.com]

  […] disease, hemolytic anemia and in patients with increased red blood cell production) May also reveal megaloblasts and hypersegmented neutrophils (containing 5 lobes in > 5% neutrophils or containing 6 or more lobes) May show red blood cells with multiple Howell-Jolly [pathologyoutlines.com]

• Bone Marrow with Hyperplasia

  marrow Normoblastic hyperplasia Absent hemosiderin Decreased sideroblasts (less than 10%) Normoblasts are smaller than normal with ragged rims of cytoplasm containing little h... [5minuteconsult.com]

The treatment of megaloblastic anemia depends on the cause [9].

• Drug-induced megaloblastic anemia is treated by discontinuation of the offending agent.
• In patients in whom the cause is unknown, treatment involves administration of folate and cobalamin.
• Because megaloblastic anemia takes years to develop, most individuals are able to adjust to the low levels of hemoglobin. Blood transfusions are rarely required for treatment of megaloblastic anemia and are usually given to in patients who are symptomatic from severe life-threatening anemia that has failed to respond to folate and cobalamin.
• Even though several formulas of cobalamin exist, only the oral and IM formulas are recommended. The effectiveness of oral cobalamin for treatment of people with severe neurological deficit has not been proven and hence only the IM formula should be used. IV cobalamin is not recommended for clinical use as the majority of the supplement is rapidly excreted by the kidneys. In addition, the IV formula can also elevate blood pressure and it is prohibitively expensive. Cobalamin has also been associated with hypersensitive reactions which are felt to be due to other chemicals in the preparation. The dose of cobalamin depends on the severity of neurological or mental symptoms and the treatment is for life. Oral cobalamin is preferred in patients with bleeding disorders to avoid hematoma formation from the IM injection. Injections are preferred in patients with neurological symptoms and those who have difficulty absorbing (eg. after gastrectomy) the supplement. Overall, oral cobalamin is preferable and much cheaper than an IM injection.
• Folate like cobalamin can be administered orally or parenterally. Elderly people, patients with end stage renal disease and women who are pregnant or breast feeding should take folate orally on a regular basis. Folate supplements are also recommended in patients with psoriasis, exfoliative dermatitis, hyperhomocysteniemia and chronic hemolytic anemia.

Today many foods including cereals are fortified with folic acid supplements to reduce risk of malignancies (eg. colon, pancreas). However, it is important to note that fortifying foods with folate can lead to cobalamin-induced neuropsychiatric disorders. It is vital that no patient be started on only folate therapy in a patient with megaloblastic anemia until cobalamin deficiency has been ruled out. Giving only folate to improve the anemia will not correct the neuropsychiatric symptoms of cobalamin deficiency and can in fact worsen them. If not sure, both folate and cobalamin should be administered if cobalamin deficiency cannot be ruled out.

Once treatment has started, all patients need follow up and monitoring to determine if improvements occurring in the blood tests and clinical exam.

• Continued elevation of LDH levels is indicative of therapy failure, continued development of iron deficiency anemia or an error in the primary diagnosis.
• Blood work will usually reveal elevation in reticulocytes within days after starting therapy. Levels of platelets and leukocytes will be normal within days but hypersegmented neutrophils may persist for 1 to 2 weeks.
• The level of hemoglobin usually increases gradually and if normal hemoglobin level is not restored within 6 to 8 weeks another cause of anemia should be considered.
• Hypokalemia is common during treatment with folate or cobalamin in patients with megaloblastic anemia and can lead to serious arrhythmias. Thus, potassium levels should be closely monitored and supplements administered.
• Because there is a sudden increase in synthesis of red blood cells, iron deficiency anemia can occur during treatment of megaloblastic anemia, thus some patients may also need iron supplementation if there is a drop in hemoglobin levels.
• The primary cause of cobalamin or folate deficiency should be addressed as recommended.

In individuals in whom the cause of megaloblastic anemia is temporary and is known, the prognosis is good. Patients with unknown diagnosis are at risk for developing anemia related complications and hypokalemia during treatment. If the cobalamin deficiency is missed or not appropriately treated, patients can develop permanent neuropsychiatric manifestations including subacute combined degeneration of the spinal cord. Pregnant women who do not take folate supplements are at risk for giving birth the infants with neural tube defects.

The most common causes of megaloblastic anemia open link are deficiencies of vitamin B12 and/or folic acid. Cobalamin deficiency may be caused by:

• Consuming a strict vegetarian diet that is restricted in dairy products, eggs and no meat products
• Atrophic gastritis 
• Achlorhydria 
• Absence or deficiency of intrinsic factor which is seen for example in pernicious anemia or congenital intrinsic factor deficiency
• Pancreatic insufficiency 
• Zollinger-Ellison syndrome
• Gastrointestinal tract disorders like inflammatory bowel disease
• Lymphoma 
• Celiac disease
• Tropical sprue
• Ileal resection
• Blind loop syndrome
• Scleroderma 
• Intestinal strictures
• Diverticulosis
• Ingestion of the fish tapeworm, Diphyllobothrium latum
• Prolonged exposure to nitrous oxide has been associated with megaloblastic anemia due to inactivation of cobalamin due to oxidative stress
• Medications associated with megaloblastic anemia include sulfonamides, methotrexate, metformin, acyclovir, zidovudine and phenformin [4]

Stores of folate are limited and deficiency can develop in a matter of weeks if there is complete cessation of folate intake. Folate deficiency causes include:

• Poor preparation of foods such as excessive heating can inactivate folate
• Deficient intake
• Increased need during for example pregnancy, lactation, rapid growth, parenteral nutrition and psoriasis
• Inflammatory bowel disease 
• Amyloidosis
• Chronic alcoholism
• Tobacco smoking
• Medications that can cause folate deficiency include metformin, phenytoin, phenobarbital, methotrexate, oral contraceptives, trimethoprim sulfamethoxazole, sulfonamides, and valproic acid

Globally the most common cause of megaloblastic anemia is ill preparation of foods containing folate. The incidence of megaloblastic anemia is most common in countries where there is malnutrition and in countries where routine administering of folate to pregnant women and elderly individuals is not common.

Vitamin B12 is chiefly obtained from sea foods, meat and dairy products. Fruits and vegetables do not contain significant amounts of this vitamin. Vitamin B12 plays a vital role in numerous biochemical reactions in the body. It is critical for the process of myelination. Cobalamin deficiency can lead to abnormal myelination which can affect the spinal cord.

Unlike vitamin B12, folate is found in large amounts in fruits, vegetables and animal protein. Because most available dietary folate is in a conjugated form, it needs to be converted to dihydrofolic acid so that it can be absorbed; folate is readily absorbed from the small intestine and does not require the presence of intrinsic factor.

In megaloblastic anemia, there is decreased deoxythymidine triphosphate (dTTP) synthesis resulting in impairment in the synthesis of DNA, RNA and protein. The red blood cells (RBCs) that are produced show slowed nuclear maturation whereas cytoplasmic maturation is relatively unaffected. There is also rapid destruction of defective RBCs in the bone marrow. The impaired production and increased destruction of RBCs in the bone marrow results in anemia. Direct interference of DNA synthesis causing megaloblastic anemia may also occur due to HIV infections and myelodysplastic disorders. 

The uptake of cobalamin is from the intestine is a complex process. Ingested cobalamin initially binds in a nonspecific manner the protein molecules in food. In the presence of gastric acidity, the cobalamin is released and then binds to R-proteins that protect it from degradation by the intestinal enzymes and secretions. This cobalamin-R protein complex then reaches the terminal ileum where it requires the presence of intrinsic factor to be absorbed into the systemic circulation. The complex is then absorbed in the terminal ileum and then transported to the bone marrow [3]. Because cobalamin is stored in the body and very little cobalamin is required on a daily basis, deficiency of this vitamin can take several years to develop. On the other hand, folate is not stored and hence deficiency usually occurs in a matter of weeks after dietary intake is discontinued.

There are many causes of megaloblastic anemia and not all can be prevented. However, in patients with a strict vegetarian diet, supplements of folate and cobalamin should be recommended. In addition, these individuals should be educated on eating foods that are fortified with these supplements and also learn how to prepare foods. Examples of foods with high levels of folate include broccoli, asparagus, lettuce, spinach, bananas, liver, melons and mushrooms. To prevent loss of folate from foods, dilution in large amounts of water and excessive heating should be avoided. After discharge all patients must be monitored to ensure that the anemia is resolving. Periodic testing of hemoglobin, LDH, indirect bilirubin levels and blood smear is recommended.

Megaloblastic anemia is a hematological disorder where certain cells of the bone marrow have arrested during the phase of nuclear maturation. These large cells are referred to as megaloblasts and can be easily seen on a blood smear. Megaloblastic anemia can be associated with diverse clinical manifestation ranging from personality changes, neurological deficits, glossitis and pancytopenia. Asides from medications, folic acid deficiency and vitamin B12 deficiency are the most common causes of this anemia. Any process that interferes with absorption of cobalamin or folate from the intestine can potentially cause the disorder.

The condition is seen globally but most common in people with restricted diets and in presence of malnutrition. It is important to note that megaloblastic anemia that occurs with either folate or cobalamin deficiency can present with almost identical signs and symptoms, but the latter is also associated with subacute combined degeneration of the spinal cord. Adults usually require at least 5-7 microgram of cobalamin and about 0.4 mg of folate per day [1] [2].

Megaloblastic anemia is a type of blood disorder that results in abnormal cells in the blood circulation and bone marrow. Megaloblastic anemia can occur because of deficiency in folate or vitamin B12. Most people develop this type of anemia either because they have a deficient diet or they are unable to absorb the vitamin from the intestine.

Megaloblastic anemia can present with a variety of symptoms that include a red painful tongue, changes in personality, difficulty with balance and walking, burning or numbness in the legs, pale skin, weight loss and weakness.

The diagnosis of this anemia can be made by looking at a blood smear or performing other blood tests that can look at levels of the vitamins. Once diagnosed, treatment is required. If the treatment with folate and vitamin B12 is done promptly, the symptoms do reverse within a few months. To prevent megaloblastic anemia, people who eat a strict vegetarian diet should take supplements of folate and vitamin B12. Foods high in folate include broccoli, liver, melons and spinach. All women who get pregnant should take folate supplements to avoid developing spinal cord problems in the infant.

1. Baumgartner MR. Vitamin-responsive disorders: cobalamin, folate, biotin, vitamins B1 and E. Handb Clin Neurol. 2013;113:1799-810.
2. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013 Jan 10;368(2):149-60
3. Nielsen MJ, Rasmussen MR, Andersen CB, Nexø E, Moestrup SK Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol. 2012 May 1;9(6):345-54
4. Shander A, Javidroozi M, Ashton ME. Drug-induced anemia and other red cell disorders: a guide in the age of polypharmacy. Curr Clin Pharmacol. 2011 Nov;6(4):295-303
5. Hooper M, Hudson P, Porter F, McCaddon A. Patient journeys: diagnosis and treatment of pernicious anaemia Br J Nurs. 2014 Apr 10-23;23(7):376-81.
6. Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev. 2014 Apr-May;13(4-5):565-8
7. Oberley MJ, Yang DT. Laboratory testing for cobalamin deficiency in megaloblastic anemia. Am J Hematol. 2013 Jun;88(6):522-6.
8. Annibale B, Lahner E, Fave GD. Diagnosis and management of pernicious anemia. Curr Gastroenterol Rep. 2011 Dec;13(6):518-24.
9. Stover PJ. Vitamin B12 and older adults. Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):24-7