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Fifth stage
Pediatric
Lec. 2
.د
انور
12/4/2017
Megaloblastic anemias
MA
Folate deficiency
Etiology
MA is very rare indeed in children but when it does
occur it is most commonly due to folate deficiency. Unlike iron, folate stores are relatively
labile and in constant need of replenishment.
Folates are required for nucleic acid synthesis and 1-carbon unit transfer in all cells of the
body, particularly growing tissues.
MA occurs after 2–3 months on a folate-free diet.
Rapid growth, fever, infection, diarrhea or hemolysis all increase folate requirements and
may further deplete the stores to the level of clinical deficiency.
Folate is absorbed in the upper jejunum by an active transport mechanism that is impaired
in malabsorption states, particularly celiac syndrome.
Various drugs are associated with deficiency of folate, e.g. phenytoin, barbiturates,
methotrexate, and TMP.
Maternal folate deficiency predisposes to neural tube defects and possibly to other
congenital abnormalities including Down syndrome.
Congenital deficiencies of several enzymes in the folate pathway are described.
Clinical features and diagnosis
The presentation, like many hematological disorders, is nonspecific.
Folate deficiency will produce macrocytosis (which can be masked by associated iron
deficiency in conditions with malabsorption); more severe forms will be associated with
leucopenia and thrombocytopenia.
Hyper segmented neutrophils on the blood film is an important clue. Serum and red cell
folate levels should be requested to confirm the Dx
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Treatment
It is straightforward with oral folic acid in a dose of 1–5 mg/d & should be continued for
several months. Where demand for folate remains high (e.g. in chronic HA) lifelong
supplementation may be required. There is often a dramatic clinical response within a few
days with a reticulocytosis by the end of a week.
Vitamin B12 deficiency
It is very rare indeed in childhood. The infant usually has an insidious onset of pallor,
lethargy and anorexia, often with neurological symptoms. With the popularity of
vegetarianism, maternal dietary deficiency may produce profound deficiency in infancy
with neurological sequelae and is currently the commonest cause of infantile B12
deficiency. It may occur in older children as part of a more generalized GIT disease with
malabsorption.
B12 deficiency has been reported in infants whose mothers have undergone gastric bypass
procedures for obesity, and those whose mothers are in the early stages of traditional
pernicious anemia. B12 deficiency occurs in early infancy due to congenital defects in the
absorption or metabolic pathway.
The diagnosis should be considered in any infant who develops pancytopenia with MA in
the first 3 years of life.
Diagnosis
The blood picture is indistinguishable from folate deficiency – there is often a pancytopenia
with macrocytosis. The serum vitamin B12 level will be low.
Treatment
The usual dose of vitamin B12 (as hydroxocobalamin) for children is 100 μg, given
intramuscularly, three times a week until the hemoglobin is normal, followed by 100 μg
monthly thereafter. Some disorders may be successfully treated with oral B12 therapy. The
neurological defects may take longer to recover.
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Congenital pure RBC aplasia (Diamond-Blackfan syndrome)
a lifelong disorder, usually presents in the first few months of life or at birth with severe
anemia and mild macrocytosis or a normocytic anemia. It is due to a deficiency of BM red
blood cell precursors.
More than a third of patients have short stature. Many pts respond to corticosteroid
treatment, but must receive therapy indefinitely. Pts who do not respond to steroid
treatment are transfusion dependent and are at risk of the multiple complications of long-
term transfusion therapy, especially iron overload.
These pts have a higher rate of developing leukemia or other hematologic malignancies
than the general population.
Transient Erythroblastopenia of Childhood(TEC)
A normocytic anemia caused by suppression of RBC synthesis, usually appears after 6
month of age in an otherwise normal infant.
Viral infections are thought to be the trigger, although the mechanism leading to RBC
aplasia is poorly understood. The onset is gradual, but anemia may become severe.
Recovery usually is spontaneous.
Differentiation from Diamond-Blackfan syndrome, in which erythroid precursors also are
absent or diminished in the BM, may be challenging. Transfusion of packed RBCs may be
necessary if the anemia becomes symptomatic before recovery.