Page 621 - Hematology_ Basic Principles and Practice ( PDFDrive )

530 Part V Red Blood Cells

of cobalamin. Therefore all vegetarians are in various stages of vertical intergenerational transfer of a deficient “bank balance” of miner-
progressive cobalamin depletion and moving inexorably toward als and micronutrients from one generation to another has been docu-
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cobalamin deficiency. This warrants early supplementation with mented in all developing countries. These affected children with
cobalamin. preexisting depleted stores of cobalamin, folate (and iron), and
In addition, the vast majority of those living in developing imminent deficiency, who are the unwitting victims of circumstance,
countries subsist on a monotonous diet that is intrinsically low in limp on through life with cognitive dysfunction and lower intelligence
animal-source foods (which are more expensive than plant-based quotient and emotional intelligence (when compared with their
diets). Although they are not strictly considered vegetarians, these better nourished counterparts in developed countries). When they
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individuals are better classified as “near-vegetarians” and should move on into adolescence and (often premature) young motherhood,
also be supplemented with cobalamin. Thus cobalamin deficiency has they pass on their deficient “bank balances” vertically to the next
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been widely reported among 45% of Northern Chinese women, generation and so the cycle continues ad infinitum. The number of
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and up to 85% of adolescents and 65% of newborns in India. such affected individuals worldwide is probably in the hundreds of
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In one series from Pakistan, among those with megaloblastic millions.
anemia (hemoglobin <8 g/dL), nearly 80% had cobalamin deficiency. Recent longitudinal studies from the West among women who
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Koreans also do not consume sufficient animal-source proteins. apparently consume a balanced nonvegetarian diet confirm that
Surprisingly, even those consuming Mediterranean diets that are rich pregnancy places an additional stress on the mother’s cobalamin
in fruits and vegetables but low in animal-source protein are at risk stores and can lead to metabolic evidence of cobalamin deficiency. 160–162
for cobalamin deficiency; among 180 pregnant women, cobalamin This can negatively affect their breastfed infants’ cobalamin status at
deficiency was found in 72% of mothers and 41% of babies. 144 6 weeks; indeed, over two-thirds of Norwegian infants of otherwise
The fetus is dependent on the mother’s cobalamin stores for a healthy mothers had a metabolic profile consistent with cobalamin
sufficient quota of cobalamin at birth; a close correlation exists deficiency, which reverted to normal after cobalamin replenish-
between low maternal serum and breast milk cobalamin concentra- ment. 161,162 Among infants with only minor developmental delays and
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tions and cobalamin insufficiency in the infant. Therefore when feeding difficulties (regurgitation) and biochemical evidence of
mothers do not consume sufficient amounts of animal-source foods, cobalamin deficiency, those who were treated with cobalamin
they themselves are at risk for nutritional cobalamin deficiency, and responded with significant clinical benefit, a fact that underscores the
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their infants will have smaller stores of the vitamin at birth. 146,147 importance of cobalamin in postnatal neurodevelopment. Thus it
Although the dictum is that infants should be exclusively breastfed is likely that many more breastfed infants in the West probably need
for the first 6 months of life, a large percentage of mothers in develop- cobalamin supplements early in life, as do their mothers in prepara-
ing countries had evidence of cobalamin deficiency. 7,148,149 For tion for pregnancy. 11
example, three-quarters of a cross section of 366 pregnant urban
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women in South India had cobalamin deficiency. So there is an
imperative to raise these values in women and in babies. An important Intragastric Events Leading to
series of studies has shown that treatment of the mother during Cobalamin Malabsorption
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pregnancy or even the infant shortly after delivery will promptly
reverse preexisting cobalamin deficiency. 152
Cobalamin-deficient infants can present with a spectrum of Inadequate Dissociation of Cobalamin
clinical findings, ranging from feeding difficulties and refusal of from Food Protein
both breast milk and complementary food by regurgitation (which
results in failure to thrive) to motor and social retardation, reflecting Dietary cobalamin is bioavailable only after proteolytic digestion of
a developmental delay. The child is persistently drowsy and rarely food by gastric acid and pepsin. Failure to release cobalamin from
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sits up or makes eye contact. There may be lemon-tint jaundice food protein can lead to food-cobalamin malabsorption and frank
with hypotonia, insufficient head control, and delayed spontaneous cobalamin deficiency despite the presence of IF. 22
turning. There can be brownish-black areas of hyperpigmentation in
the dorsal fingers and toes as well as over the medial thighs, arms, and
axillae (which usually resolve within 3 months of therapy). Evidence Congenital Intrinsic Factor Deficiency
of megaloblastic anemia may be masked with superimposed iron
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deficiency. If left untreated, there is growth retardation with reduced Congenital IF deficiency arising from mutations in gastric IF,
height and weight, and reduced head circumference with cranial resulting in complete loss of IF, can be transmitted as an autosomal
magnetic resonance imaging (MRI) showing delayed myelination and recessive trait and expressed in homozygotes by the age of 2 years as
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frontoparietal cortical atrophy in affected infants ; these can also severe megaloblastic anemia (less than 100 cases reported). Dys-
be reversed within 3 months of cobalamin replacement. Treatment functional IF may lead to only a mild abnormality in binding to
results in a dramatic increase in alertness and responsiveness of the cobalamin and result in a delayed presentation into the second
child, who is now miraculously transformed into a normal child who, decade.
within a few days, rolls over spontaneously, makes eye contact with
its mother, and is much more interested in the surroundings. Any
previous abnormal movements (tremors, chorea, or myoclonus) may Loss or Atrophy of Gastric Oxyntic Mucosa
regress but transiently return within a few days to affect the face or
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tongue; however, these will resolve in 2 to 3 months. Cobalamin IF deficiency, which arises from atrophy of gastric parietal (oxyntic)
deficiency often resurfaces during wartime, which invariably leaves mucosal cells, can be caused by total or partial gastrectomy; by
women and their infants malnourished. 155 autoimmune destruction, as observed in adult Addisonian pernicious
Infants in the West fed a macrobiotic diet (vegan-like with occa- anemia or, rarely, in a similar disease in children (juvenile pernicious
sional servings of fish) must be rapidly replenished with cobalamin anemia); and after destruction of gastric mucosa by caustic (lye)
before switching to a cobalamin-rich diet. Otherwise, up to 20% ingestion.
continue to have low cobalamin status, which can lead to impaired Total gastrectomy invariably leads to cobalamin deficiency in
psychomotor functioning well into youth and later adolescence with about 5 years (range, 2 to 10 years); indeed, longitudinal follow-up
compromise in faculties related to reasoning, abstract thinking, and revealed that all 176 patients developed cobalamin deficiency within
learning ability. 156 4 years, with earlier clinical presentations occurring in those with
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When children in resource-limited settings grow up on the same lower cobalamin status preoperatively. This condition is often
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monotonous diet as their parents, they are at risk for combined associated with iron deficiency, warranting routine cobalamin and
cobalamin, folate (and iron) deficiency. 7,114,157–159 This problem of iron replacement prophylactically.