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Folate-Deficiency Anemia

Folate Deficiency Anemia

Folate-deficiency anemia frequently appears in women of childbearing age, in those who are pregnant or lactating, in alcohol abusers and malnourished individuals, thus proving the necessity of folate oral supplementation. Prevention must be carefully conducted, since the elderly may have difficulties tolerating folate intake.


Presentation

Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features. When faced with a patient suffering from this condition, the physician must spend time on history inquiry in order to determine if the individual has risk factors like the use of certain drugs (e.g. methotrexate, sulfonamides, or phenytoin) or suffers from other diseases, such as malabsorption syndromes and chronic hemolytic anemia. Patients address their physician for tongue pain and ulcerations or angular stomatitis, vomiting, anorexia, weight loss, abdominal pain and diarrhea that usually occur after food intake. Hair pigmentation may also change. Neurologic symptoms include depression, impaired abstraction performance [1], a diminished cognitive status that may progress to dementia [2]. Keeping in mind that some studies have shown that folate deficiency may be associated with cervical, esophageal, and colon cancer, as well as ulcerative colitis [3], the physician must inquire about symptoms related to these illnesses, too. Heart disease signs must also be searched for, knowing that low folate intake increases the risk of coronary artery disease [4] [5]. Pregnant women must be closely monitored regarding folate-deficiency anemia signs because folate deficiency is known to cause neural tube birth defects, preterm delivery, growth retardation, and low birth weight [6].

Oral cavity examination frequently reveals a red, swollen, and shiny tongue. Some patients are subfebrile although infection is excluded and present with patchy hyperpigmented areas of the skin and mucous membranes. Their typical location includes dorsal aspects of the toes and fingers, as well as creases of soles and palms.

Anemia
  • Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features.[symptoma.com]
  • Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification.[ncbi.nlm.nih.gov]
  • Folate deficiency anemia, unspecified D53 Other nutritional anemias D53.0 Protein deficiency anemia D53.1 Other megaloblastic anemias, not elsewhere classified D53.2 Scorbutic anemia D53.8 Other specified nutritional anemias D53.9 Nutritional anemia,[icd10data.com]
  • NIH: National Heart, Lung, and Blood Institute Anemia (Medical Encyclopedia) Anemia - B12 deficiency (Medical Encyclopedia) Anemia caused by low iron -- infants and toddlers (Medical Encyclopedia) Anemia of chronic disease (Medical Encyclopedia) Anemia[icdlist.com]
Fatigue
  • Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features.[symptoma.com]
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019[patientslikeme.com]
  • Symptoms of folic acid deficiency include: fatigue mouth sores gray hair swollen tongue poor growth (also among the chief symptoms of malnutrition) Once anemia occurs, you might experience the following: fatigue dizziness feeling cold irritability headache[healthline.com]
  • They include paleness, fatigue, shortness of breath, and palpitations, or heart fluttering, particularly if you exert yourself. In both disorders, your mouth and tongue may be sore, and your skin may become yellow in color.[revivelifelab.com]
Weight Loss
  • Patients address their physician for tongue pain and ulcerations or angular stomatitis, vomiting, anorexia, weight loss, abdominal pain and diarrhea that usually occur after food intake. Hair pigmentation may also change.[symptoma.com]
  • loss diets Folic acid is needed to help a baby in the womb grow properly.[nlm.nih.gov]
  • Other folic acid deficiency symptoms are: Loss of appetite Weight loss Gray hair Depression Diarrhea Poor growth Headache Irritability The primary cause of folic acid deficiency anemia is malnutrition.[gleneaglesglobalhospitals.com]
  • Any kind of anemia can cause problems like: Fatigue Lack of energy Feeling short of breath Headaches Pale skin Racing heart Weight loss or not feeling hungry Ringing in your ears If your anemia is caused by not having enough folate in your body, you could[webmd.com]
Pallor
  • When to seek medical advice Call your child's healthcare provider right away if any of these occur: Your child refuses to eat or has trouble eating You child has a stomachache, diarrhea, or bloating Symptoms continue or get worse Pallor does not improve[fairview.org]
  • For more information see: Folic acid and birth defect prevention Symptoms Fatigue Headache Pallor Sore mouth and tongue Exams and Tests The doctor or nurse will perform a physical exam.[lutheranhealthcare.org]
  • Symptoms may include: Fatigue Weakness Headache Pallor Sore mouth and tongue The goal is to identify and treat the cause of the folate deficiency.[nlm.nih.gov]
  • Symptoms Symptoms may include: Fatigue Headache Pallor Sore mouth and tongue Exams and Tests The health care provider will perform a physical exam.[ufhealth.org]
Epilepsy
  • Use of safe drugs, especially drugs that limit the absorption of folic acid such as bacbituric, anticonvulsants, drugs for epilepsy, antimalarial drugs, anti-metabolism drugs, In areas where a high prevalence of anemia is present in pregnant women, supplementation[hellodoktor.com]
  • In a prospective study of women with epilepsy, folic acid levels decreased with increasing plasma AED levels and with the number of AEDs.[epilepsy.com]
  • Epilepsy . Taking folic acid does not reduce seizures in people with epilepsy . Esophageal cancer . Research suggests that consuming more folate in the diet lowers the risk for developing esophageal cancer .[emedicinehealth.com]
  • You are taking certain medication for epilepsy (your doctor will advise). See also the separate leaflets called Planning to Become Pregnant and Diet and Lifestyle during Pregnancy .[patient.info]
Dyspnea
  • Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features.[symptoma.com]
  • 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]
Loss of Appetite
  • Other folic acid deficiency symptoms are: Loss of appetite Weight loss Gray hair Depression Diarrhea Poor growth Headache Irritability The primary cause of folic acid deficiency anemia is malnutrition.[gleneaglesglobalhospitals.com]
  • Symptoms of Folic Acid Deficiency Anemia Severe fatigue and weakness Paleness (pallor) Shortness of breath Heart palpitations or noticeably rapid heartbeat upon exertion Sore, red, and glazed-looking tongue Loss of appetite leading to weight loss Abdominal[healthcommunities.com]
  • […] of appetite difficulty concentrating Factors that increase your likelihood of developing this condition include: eating overcooked foods consuming a vitamin-poor diet heavy alcohol drinking (alcohol interferes with folate absorption) medical conditions[healthline.com]
  • People with a folate deficiency will show obvious physical signs like weight loss and loss of appetite. Folate deficiency is also known to cause sore tongue, headache, and irritability.[newsmax.com]
Nausea
  • Increased destruction: superoxide can inactivate folate Clinical features Symptoms due to anemia: weakness, fatigue, difficulty concentrating, irritability, headache, palpitations, shortness of breath, cardiac failure Gastrointestinal symptoms: anorexia, nausea[pathologyoutlines.com]
  • High folic acid dosage causes: Abdominal cramps Diarrhea Rash Sleep disorders Irritability Confusion Nausea Upset stomach Behavioral changes Seizures Due to anemia, you may have weakness and fatigue.[gleneaglesglobalhospitals.com]
  • Nausea from morning sickness, anorexia, and poor dietary habits also contribute to folate deficiency during pregancy. There is an association between folate deficiency during pregnancy and neural tube defects in the developing fetus.[medcentral.org]
  • Signs & Symptoms Blackheads (black spots the size of a pinhead); Fatigue and weakness; Paleness; Red, sore tongue; Shortness of breath; Nausea, vomiting and diarrhea (rare); Neurologic abnormalities – only in infants.[rxmed.com]
  • Folic Acid Deficiency Anemia Severe fatigue and weakness Paleness (pallor) Shortness of breath Heart palpitations or noticeably rapid heartbeat upon exertion Sore, red, and glazed-looking tongue Loss of appetite leading to weight loss Abdominal swelling Nausea[healthcommunities.com]
Vomiting
  • Patients address their physician for tongue pain and ulcerations or angular stomatitis, vomiting, anorexia, weight loss, abdominal pain and diarrhea that usually occur after food intake. Hair pigmentation may also change.[symptoma.com]
  • […] destruction: superoxide can inactivate folate Clinical features Symptoms due to anemia: weakness, fatigue, difficulty concentrating, irritability, headache, palpitations, shortness of breath, cardiac failure Gastrointestinal symptoms: anorexia, nausea, vomiting[pathologyoutlines.com]
  • Signs & Symptoms Blackheads (black spots the size of a pinhead); Fatigue and weakness; Paleness; Red, sore tongue; Shortness of breath; Nausea, vomiting and diarrhea (rare); Neurologic abnormalities – only in infants.[rxmed.com]
  • Deficiency Anemia Severe fatigue and weakness Paleness (pallor) Shortness of breath Heart palpitations or noticeably rapid heartbeat upon exertion Sore, red, and glazed-looking tongue Loss of appetite leading to weight loss Abdominal swelling Nausea, vomiting[healthcommunities.com]
  • Morning sickness that results in vomiting can cause you to lose folic acid. Malabsorption Malabsorption occurs when your body can’t properly absorb a vitamin or mineral.[healthline.com]
Sore Mouth
  • For more information see: Folic acid and birth defect prevention Symptoms Fatigue Headache Pallor Sore mouth and tongue Exams and Tests The doctor or nurse will perform a physical exam.[lutheranhealthcare.org]
  • Symptoms may include: Fatigue Weakness Headache Pallor Sore mouth and tongue The goal is to identify and treat the cause of the folate deficiency.[nlm.nih.gov]
  • Symptoms Symptoms may include: Fatigue Headache Pallor Sore mouth and tongue Exams and Tests The health care provider will perform a physical exam.[ufhealth.org]
  • Symptoms may include: Fatigue Weakness Headache Pallor Sore mouth and tongue Exams and Tests The health care provider will perform a physical exam.[baptistjax.com]
Irritability
  • Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features.[symptoma.com]
  • High folic acid dosage causes: Abdominal cramps Diarrhea Rash Sleep disorders Irritability Confusion Nausea Upset stomach Behavioral changes Seizures Due to anemia, you may have weakness and fatigue.[gleneaglesglobalhospitals.com]
  • […] iron, folic acid or vitamin B12 Blood disorders such as sickle cell anemia and thalassemia, or cancer Aplastic anemia, a condition that can be inherited or acquired G6PD deficiency, a metabolic disorder Anemia can make you feel tired, cold, dizzy, and irritable[icdlist.com]
  • , chronic alcoholism (increased excretion of folate into bile), hemodialysis (may have excess folate loss) Increased destruction: superoxide can inactivate folate Clinical features Symptoms due to anemia: weakness, fatigue, difficulty concentrating, irritability[pathologyoutlines.com]
Headache
  • Folate-deficiency anemia causes symptoms that are common for all types of anemia, like fatigue, irritability, headaches, diminished concentration ability, dyspnea, and palpitations, but also has certain supplementary features.[symptoma.com]
  • You may be short of breath or have a headache. Your doctor will diagnose anemia with a physical exam and blood tests. Treatment depends on the kind of anemia you have.[icdlist.com]
  • […] alcoholism (increased excretion of folate into bile), hemodialysis (may have excess folate loss) Increased destruction: superoxide can inactivate folate Clinical features Symptoms due to anemia: weakness, fatigue, difficulty concentrating, irritability, headache[pathologyoutlines.com]
  • For more information see: Folic acid and birth defect prevention Symptoms Fatigue Headache Pallor Sore mouth and tongue Exams and Tests The doctor or nurse will perform a physical exam.[lutheranhealthcare.org]
Peripheral Neuropathy
  • neuropathy, and memory loss).[icid.salisbury.nhs.uk]
  • Nerve pain (peripheral neuropathy) . There is conflicting evidence about the role of folic acid in nerve pain for people with diabetes ( diabetic neuropathy ).[emedicinehealth.com]
  • Neurological symptoms (eg, paraesthesia, numbness, cognitive changes, visual disturbance) are more typical of vitamin B12 deficiency but patients with folate deficiency may report mild symptoms of peripheral neuropathy or psychiatric disturbance (eg,[patient.info]
  • neuropathy ), particularly in the legs If neurological problems do develop, they may be irreversible.[nhsdirect.wales.nhs.uk]
Paresthesia
  • Patients with vitamin B 12 deficiency may describe paresthesias related to peripheral neuropathy, poor or strict vegan diet, lack of socioeconomic resources, bowel-related symptoms (including diarrhea), or a history of bowel surgery for weight loss.[aafp.org]
  • The more common neurologic symptoms are paresthesias, numbness, and ataxia, although dementia and psychosis may occur. 7 Although hematologic abnormalities frequently develop before the onset of neurologic disease, more than one quarter of patients with[jamanetwork.com]

Workup

Blood workup should include a complete blood count, demonstrating the presence of megaloblastic anemia. The mean corpuscular volume is typically increased (above 96 fL ). A blood smear will show macrocytes, hypersegmented polymorphs, leukopenia, and thrombocytopenia if the deficiency is severe enough. In extreme cases, pancytopenia can be observed. The next step is to demonstrate folate deficiency and that is achieved by measuring folate levels. Cobalamin serum levels should also be measured in order to exclude cobalamin deficiency. Blood homocysteine will be found increased, above the reference range of 5-16 mmol/L, but it can be influenced by other factors, like kidney disease [7]. Folate levels can also be measured in the red blood cells by radioisotope dilution, but this value is considered to be less reliable because it offers information about the folate status over the lifetime of the erythrocytes, whereas short term folate status is reflected by its serum level [8]. A bone marrow biopsy will demonstrate megaloblastic cell maturation. Liver function tests and thyroid function tests are useful in cases where undeclared alcohol abuse or hypothyroidism are suspected, respectively. Malabsorptive disorders, if suspected, should be thoroughly searched for.

Macrocytosis
  • Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic.[ncbi.nlm.nih.gov]
  • However, this concept remains useful for identifying the most predominant etiology for macrocytosis.[aafp.org]
  • […] with anaemia but those patients who have macrocytosis with anaemia should have vitamin B12 and folate measurements performed. 2.2.2 Macrocytosis The level of macrocytosis can predict the probability of vitamin B12 and folate deficiency being present.[icid.salisbury.nhs.uk]
Macrocytic Anemia
  • Definition / general Folate deficiency is a low level of folic acid (Vitamin B9) in the body Essential features Characterized by macrocytic anemia Terminology Also called Vitamin B9 deficiency Pathophysiology Etiology Inadequate ingestion of folate containing[pathologyoutlines.com]
  • ) anemia caused by a lack of folic acid in the diet. folic acid deficiency anemia Anemia resulting from a deficiency of folic acid.[medical-dictionary.thefreedictionary.com]
  • Folate deficiency is one of the causes of macrocytic anemia.[epilepsy.com]
  • Antibodies against the proteins of cells involved can be helpful in the diagnosis of macrocytic anemia. Anti-intrinsic factor antibodies, are fairly specific, but unfortunately, not sensitve.[med-ed.virginia.edu]
  • Algorithm for the evaluation of macrocytic anemia. (RBC red blood cell; MMA methylmalonic acid.) Evaluation of Macrocytic Anemia Figure 3. Algorithm for the evaluation of macrocytic anemia. (RBC red blood cell; MMA methylmalonic acid.)[aafp.org]
Folic Acid Decreased
  • Recent studies found that supplemental vitamin B12 and folic acid decreased homocysteine levels in subjects with vascular disease and in young adult women. The most significant drop in homocysteine level was seen when folic acid was taken alone.[moyak.com]
Howell-Jolly Bodies
  • Multinucleate RBCs, abnormal karyorrhexis, increased pyknosis, and Howell-Jolly bodies ( right) may be seen.[med-ed.virginia.edu]
Megaloblastic Bone Marrow
  • 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.[rarediseases.org]
  • Defective DNA synthesis in human megaloblastic bone marrow: effects of homocysteine and methionine. J Clin Invest. 1969;48(2):284–289. 15. Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P.[aafp.org]
  • Defective DNA synthesis in human megaloblastic bone marrow: effects of homocysteine and methionine. J Clin Invest . 1969;48(2):284–289. 15. Ortiz Z, Shea B, Suarez Almazor M, Moher D, Wells G, Tugwell P.[aafp.org]

Treatment

  • Treatment Giving patients 5mg / day of folic acid can also ensure the restoration of reserves. In fact, treatment with folic acid is not dangerous because there is no risk of cumulative factors.[hellodoktor.com]
  • , or therapies expectations for the course of the disease your opinion or preference Treatment may include: vitamin and mineral supplements change in diet medication treatment of the causative disease Treatment usually involves taking an oral or injected[medcentral.org]
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you. Know why a new medicine or treatment is prescribed, and how it will help you.[mynovant.org]
  • Early treatment is needed to prevent problems such as poor reasoning and learning.[assets.cooperhealth.org]

Prognosis

  • Outlook (Prognosis) Anemia usually responds well to treatment within 2 months. Possible Complications Symptoms of anemia can cause discomfort.[lutheranhealthcare.org]
  • Outlook (Prognosis) Anemia most often responds well to treatment within 2 months. Possible Complications Symptoms of anemia can cause discomfort.[ufhealth.org]
  • Outlook (Prognosis) Folate-deficiency anemia most often responds well to treatment within 3 to 6 months. It will likely get better when the underlying cause of the deficiency is treated.[baptistjax.com]
  • Prognosis Usually reversible in three to four weeks with an adequate folic acid intake.[rxmed.com]

Etiology

  • Definition / general Folate deficiency is a low level of folic acid (Vitamin B9) in the body Essential features Characterized by macrocytic anemia Terminology Also called Vitamin B9 deficiency Pathophysiology Etiology Inadequate ingestion of folate containing[pathologyoutlines.com]
  • The most common etiologies are alcoholism, vitamin B 12 and folate deficiencies, and medications.[aafp.org]
  • Etiology The most common causes of folate deficiency are Inadequate intake (usually in patients with undernutrition or alcoholism) Increased demand (eg, due to pregnancy or lactation) Deficiency can also result from inadequate bioavailability and increased[merckmanuals.com]

Epidemiology

  • Article navigation 1From the Department of Epidemiology (OAO, RSW, DAA, and GPO) and Center for Spina Bifida Research, Prevention and Policy (GPO), Rollins School of Public Health, Emory University, Atlanta, GA; the Departments of Medicine and Oncology[ajcn.nutrition.org]
  • […] supplementation and child Asperger syndrome or pervasive developmental disorder-not otherwise specified. [6] Effects on carcinogens Diminished folate status has historically been associated with enhanced carcinogenesis. [16] As recently as 2002, authors cited epidemiologic[emedicine.medscape.com]
  • Epidemiologic evidence generally indicates that a high intake of folate-rich foods offers protection against the development of some common cancers, but the relationship between folic acid and cancer is complicated, as you’ve learned.[draxe.com]
  • Epidemiologic evidence generally indicates that a high intake of folate-rich foods offers protection against the development of some common cancers , but the relationship between folic acid and cancer is complicated, as you’ve learned.[draxe.com]
Sex distribution
Age distribution

Pathophysiology

  • Definition / general Folate deficiency is a low level of folic acid (Vitamin B9) in the body Essential features Characterized by macrocytic anemia Terminology Also called Vitamin B9 deficiency Pathophysiology Etiology Inadequate ingestion of folate containing[pathologyoutlines.com]
  • A temperature chart documenting the course of the patient's pyrexia is presented and potential pathophysiological mechanisms are proposed.[casesjournal.biomedcentral.com]
  • Understanding Pathophysiology (3rd ed.). Mosby. p. 543. ISBN 978-0-323-02368-9. Tamparo C (2011). Diseases of the Human Body (Fifth ed.). Philadelphia, PA. p. 337. ISBN 978-0-8036-2505-1. Haslam N, Probert CS (February 1998).[en.wikipedia.org]
  • Alcohol 26 65 15 36 B 12 and/or folate deficiency 6 9 28 21 Medications 37* 3 2 11 Hypothyroidism — 1 12 5 Bone marrow dysplasias 6 1 5 5 Liver disease (nonalcoholic) 6 — 2 6 Reticulocytosis 8 — — 7 Miscellaneous 3 21 13 7 Not established 7 — 22 12 Pathophysiology[aafp.org]

Prevention

  • A few of them are mentioned below: Preventing and treating low blood levels Used for memory loss Use to prevent heart disease Prevent miscarriage and birth defects Prevent hearing loss Prevents depression Treats anemia Used for kidney diseases Used in[gleneaglesglobalhospitals.com]
  • Taking 300-400 mcg of folic acid daily is commonly used during pregnancy to prevent birth defects.[emedicinehealth.com]
  • Prevention The prevention of folic acid is primarily through nutrition. It is important to know the use of appropriate food sources, especially green vegetables as well as other ingredients.[hellodoktor.com]
  • Prevention Eating plenty of folate-rich foods can help prevent this condition. Experts recommend that women take 400 micrograms (mcg) of folic acid every day before they get pregnant and through the first 3 months of their pregnancy.[lutheranhealthcare.org]
  • Preventive Services Task Force (2009). Folic acid to prevent neural tube defects. Available online: . Credits By Healthwise Staff Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine Adam Husney, MD - Family Medicine Martin J.[northshore.org]

References

Article

  1. La Rue A, Koehler K, Wayne S, et al. Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment. Am J Clin Nutr. 1997;65:20–29.
  2. Stokstad EL, Chan MM, Watson JE, et al. Nutritional interactions of vitamin B12, folic acid, and thyroxine. Ann N Y Acad Sci. 1980;355:119-129.
  3. Lashner B, Provencer K, Seidner D, et al. The Effect of Folic Acid Supplementation on the Risk for Cancer or Dysplasia in Ulcerative Colitis. Gastroenterology. 1997;112:29–32.
  4. Landgren F, Israelsson B, Lindgren A, et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med. 1995;237:381–388.
  5. Morrison H I, Schaubel D, Desmeules M, et al. J Am Med Assoc. Serum folate and risk of fatal coronary heart disease. 1996;275:1893–1896.
  6. Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr. 2000; 71(5): 1295S-303S.
  7. Green R. Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies. Am J Clin Nutr. 2011; 94(2): 666S-672S.
  8. Yetley EA, Pfeiffer CM, Phinney KW, et al. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(1): 303S-312S.

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Last updated: 2019-06-28 10:16