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Megaloblastic Anemia Clinical Presentation

  • Author: Paul Schick, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Apr 06, 2014


A patient’s history might reveal anemia and neurological abnormalities. Since anemia develops insidiously, patients may be virtually asymptomatic. However, other patients might experience severe anemia and, hence, weakness and cardiopulmonary impairment. A lemon-color complexion occurs due to intramedullary hemolysis. Some patients can have gastrointestinal symptoms such as loss of appetite, weight loss, nausea, and constipation. Patients may have a sore tongue and canker sores.

A spectrum of mental changes, from a change in personality to psychosis, as well as peripheral neuropathy, can occur in both folate and cobalamin deficiencies. Peripheral neuropathy presents as numbness, pain, tingling, and burning in a patient’s hands and feet. Patients may report loss of sensation and that they feel like they are wearing a thin stocking or glove.

Unsteady gait, abnormal proprioception, and loss of balance occur in subacute combined spinal cord degeneration. Some patients with cobalamin deficiency can present primarily with neurological impairment and are not anemic. Neurologic symptoms may range from mild to severe. Cobalamin deficiency should be considered even if a patient has minimal neurologic symptoms and is not anemic.

History findings to help identify a cobalamin deficiency are as follows:

  • Evidence for achlorhydria such as abdominal discomfort, reflux, early satiety, and abdominal bloating: This condition can impair cobalamin absorption.
  • Pernicious anemia: These patients may have signs of other autoimmune disorders such as thyroid disorders, type I diabetes, or Addison disease.
  • Family history, HLA (HLA A2, A3, B7, B12), and type A blood (Scandinavians and African Americans)
  • History of a gastrectomy
  • Conditions that affect the terminal ileum (site of cobalamin absorption), such as inflammatory bowel disease, sprue, or ileal resection
  • Conditions in which cobalamin is competitively consumed: History of abdominal surgery might suggest a blind loop syndrome. Exposure to raw fish might suggest D latum infestation.
  • Zollinger-Ellison syndrome or pancreatic insufficiency: There is impaired binding of cobalamin to intrinsic factor.
  • Strict vegetarian with no consumption of eggs and dairy products
  • A history of folate administration without vitamin B-12 therapy: This should alert one to the possibility of the progression of neuropsychiatric complications in a patient who is not anemic.
  • A history of megaloblastosis since childhood: This would suggest a hereditary cause of cobalamin deficiency.

History findings to help identify folate deficiency are as follows:

  • Poor nutrition, alternative diets, and excessive heating and dilution of foods
  • Chronic alcoholism
  • Conditions that interfere with folate absorption, including inflammatory bowel disease, sprue or gluten sensitivity, and amyloidosis
  • Conditions that increase folate consumption, such as pregnancy, lactation, hemolytic anemia, hyperthyroidism, and exfoliative dermatitis
  • Hyperalimentation and hemodialysis
  • Medications that affect folate (see the list in Etiology)
  • Hereditary disorder: A lifelong history of megaloblastosis or folate deficiency would suggest a hereditary disorder as the cause.

Physical Examination

Evidence of anemia: Patients may be asymptomatic if the anemia had developed gradually and was compensated. In severe anemia, patients may have dyspnea, tachycardia, and cardiopulmonary distress.

Patients may have a lemon-yellow hue due to the combination of anemia and an increased indirect bilirubin level. The source of the bilirubin is intramedullary hemolysis.

Glossitis, characterized by a smooth tongue due to loss of papillae, occurs in persons with cobalamin deficiency.

Dermatologic signs include hyperpigmentation of the skin and abnormal pigmentation of hair due to increased melanin synthesis.

A wide range of mental changes, from irritability to psychosis, as well a peripheral neuropathy, can occur in both folate and cobalamin deficiencies.

Subacute combined degeneration occurs in cobalamin deficiency. Patients who present with abnormal gait, loss of balance, speech impairment, and loss of proprioceptive and vibratory senses. Blindness due to optic atrophy may occur.

Abdominal scars may suggest a blind loop syndrome due to gastric surgery or a lack of ileal absorption of cobalamin in a patient who had an ileal resection.

Patients with nontropical and tropical sprue may have signs of malabsorption, such as weight loss, abdominal distention, diarrhea, and steatorrhea. These patients often have metabolic bone disease or bleeding resulting from to deficiencies in vitamin K–dependent factors.

Patients who have megaloblastosis as a result of HIV infection or myelodysplastic syndromes usually have signs of these disorders.

Children with inborn errors associated with folate and cobalamin deficiencies may have signs of these hereditary disorders .

Contributor Information and Disclosures

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada, American Clinical and Climatological Association, International Society of Blood Transfusion

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Thomas H Davis, MD, FACP Associate Professor, Fellowship Program Director, Department of Internal Medicine, Section of Hematology/Oncology, Geisel School of Medicine at Dartmouth

Thomas H Davis, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Education, American College of Physicians, New Hampshire Medical Society, Phi Beta Kappa, Society of University Urologists

Disclosure: Nothing to disclose.

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Megaloblastic anemia. View of red blood cells
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