Megaloblastic Anemia Clinical Presentation

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 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 folate deficiency are as follows:

• Poor nutrition, alternative diets, and excessive heating 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.

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.
• History of a gastrectomy: This would suggest the possibility of insufficient production of intrinsic factor.
• 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 and hence not available: History of abdominal surgery might suggest a blind loop syndrome. Exposure to raw fish might suggest D latum infestation.
• 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.

Evidence of anemia can include patients who are pale and weak but otherwise asymptomatic, particularly if the anemia had developed gradually and is 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 in persons 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.