Pediatric Megaloblastic Anemia Clinical Presentation

Updated: Dec 16, 2021
  • Author: James L Harper, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
  • Print


Dietary history

A careful dietary history is essential to the diagnosis of megaloblastic anemia. [12] The type and quantity of foods should be documented. In the case of a breastfed infant with megaloblastic anemia, the maternal dietary history should also be obtained.

Document dietary faddism or family-induced dietary restriction. Folate deficiency may result if the child's only source of dietary folic acid is goat's milk.

Children with one nutrient deficiency are at increased risk for other deficiencies; thus, search the history for evidence of other nutrient deficiencies.

Dietary vitamin B-12 deficiency in infants is extremely rare, but may occur in breastfed infants whose mothers are B-12 deficient. Obtain a careful history of the mother's diet. Include the mother's current diet, her diet while pregnant, and her diet before pregnancy. Vitamin B-12 deficiency is most common in women who have no meat in their diet.

Infants are of special concern owing to the impact of these deficiencies on their development and intellectual function. While it is uncommon for infants to have a dietary deficiency, if suspected, assessment of the maternal diet is key in breastfed infants.

GI disease

Carefully document the presence or absence of malabsorption syndromes, sprue, and preexisting conditions such as intestinal blind-loop syndrome or bowel resection. Evaluate for other acquired GI disorders, such as fish tapeworm infestation by Diphyllobothrium latum. Evaluate for Crohn disease and other causes of chronic inflammation of the ileum as potential causes of B-12 malabsorption. Carefully monitor for megaloblastic anemia due to impaired absorption of B-12 or folic acid following surgery involving the stomach, jejunum, or ileum.

Bone or joint pain, bruising, or bleeding

Bone and joint pain suggest that the child may have leukemia or another malignancy, with marrow replacement as the cause of pancytopenia. Bleeding and bruising are often observed in association with vitamin B-12 deficiency caused by thrombocytopenia, but these symptoms should also raise suspicion of leukemia or other marrow replacement disorders.


A history of sulfa exposure or use of antifolate antimetabolite chemotherapeutic agents, such as methotrexate, trimetrexate, or azathioprine, should be considered. Also consider the use of other antifolate drugs or drugs that affect the absorption of either folic acid or vitamin B-12. For example, certain anticonvulsants (eg, phenytoin, primidone) impair folate absorption.

Family history

Congenital absence or deficiency of carrier proteins is a common cause of vitamin B-12 deficiency. These deficiencies occur in families. Obtaining an extended family history is usually necessary to detect other affected family members. These conditions often manifest during infancy and early childhood and are rare but important causes of megaloblastic anemia because myelopathy and developmental delays occur without treatment.

Evaluate for Imerslund-Grasbeck syndrome of proteinuria and excretion of cobalamin and intrinsic factor (IF).

Diabetes mellitus

Non-type 1 diabetes mellitus is characteristic of thiamine-responsive megaloblastic anemia, with a study by Habeb et al reporting that within a patient cohort, diabetes developed at a median age of 10 months. The investigators stated that diabetes can be asymptomatic but can nonetheless present in the syndrome before other signs and symptoms do. [13]


Physical Examination

The physical examination is largely directed by the findings of the history. Common findings include glossitis, stomatitis, hyperpigmentation, and weight loss.

Look for physical evidence of anemia, thrombocytopenia, and neutropenia. Pancytopenia can be observed in megaloblastic anemia, but it should raise the suspicion of a possible malignancy.

Evaluate for lymphadenopathy, hepatosplenomegaly, and abdominal or retroperitoneal masses as evidence of a malignancy.

Carefully document the neurologic status of a child with megaloblastic anemia. Document altered mental or neurologic status. Vibratory sensation in the extremities is frequently affected in vitamin B-12 deficiency. [14] These changes may reflect neurotoxicity from deficient B-12 levels. Once documented, these symptoms can be monitored to determine the degree of resolution once the child is B-12 replete.