Download Vitamin B12 deficiency

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 mo 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 diagnosi
The presentation, like many hematological disorders, is nonspecific
Folate deficiency will produce macrocytosis (which can be masked b
associated iron deficiency in conditions with malabsorption); mor
severe forms will be associated with leucopenia and thrombocytopenia
Hypersegmented neutrophils on the blood film is an importan
clue. Serum and red cell folate levels should be requested to confirm the D
Treatmen
It is straightforward with oral folic acid in a dose of 1–5 mg/
& should be continued for several months. Where demand fo
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 b
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.
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.