Megaloblastic Anemia Clinical Presentation

Updated: Jul 17, 2021
  • Author: Srikanth Nagalla, MD, MS, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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A patient’s history might reveal manifestations of anemia and neurological abnormalities. Since anemia develops insidiously, patients may be virtually asymptomatic. However, those with severe anemia may experience weakness and cardiopulmonary impairment. A lemon-color complexion occurs due to intramedullary hemolysis. Some patients can have gastrointestinal signs and 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 Diphyllobothrium latum (fish tapeworm) infestation. [15]

  • 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. Infantile vitamin B-12 deficiency is common in underdeveloped countries and is associated with hyperpigmentation of the dorsa of hands and feet as well as generalized hyperpigmentation. [16]

.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 neurologic degeneration occurs in cobalamin deficiency. Patients 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 .