Pediatric Examination and Board Review (151 page)

11.
Which of the following is not a physical feature among patients with thalassemia major?

(A) frontal bossing

(B) splenomegaly

(C) scleral icterus

(D) tibial bowing

(E) growth failure

12.
Hemoglobin H disease is associated with how many alpha-globin gene deletions?

(A) 0

(B) 1

(C) 2

(D) 3

(E) 4

13.
Which of the following is not a complication of transfusion-associated hemochromatosis?

(A) dilated cardiomyopathy

(B) diabetes mellitus

(C) renal insufficiency

(D) hypogonadism

(E) osteoporosis

14.
Which of the following is a normal childhood hemoglobin electrophoresis pattern?

(A) 96% A, 3% A2, 1% F

(B) 90% A, 8% A2, 2% F

(C) 90% A, 2% A2, 8% F

(D) 80% A, 10% A2, 10% F

(E) 80% A, 2% A2, 18% F

15.
Which of the following statements regarding Diamond-Blackfan anemia is false?

(A) Diamond-Blackfan anemia is usually microcytic

(B) reticulocyte count in patients with Diamond-Blackfan anemia is low

(C) patients with Diamond-Blackfan anemia have abnormalities of their thumbs

(D) Diamond-Blackfan anemia is usually diagnosed in patients before their first birthday

(E) small “i” antigens are present on red blood cells

16.
Which of the following anemic patients is most likely to have transient erythroblastopenia of childhood?

(A) 2-month-old boy with macrocytic anemia

(B) 11-month-old girl with increased fetal hemoglobin levels

(C) 28-month-old boy with a history of upper respiratory infection

(D) 35-month-old girl with failure to thrive

(E) newborn with anemia and jaundice

17.
Which of the following is not a symptom of lead toxicity?

(A) recurrent emesis

(B) constipation

(C) behavioral changes

(D) polyuria

(E) anemia

ANSWERS

1.
(B)
The most likely diagnosis is iron deficiency anemia, based on the patient’s age and her history of cow’s milk intake. Iron deficiency is a common cause of anemia in children, with a peak incidence between 6 months and 3 years of age. Iron stores initially are accumulated during the last 3 months of pregnancy, and so iron deficiency in neonates and early infancy is due either to prematurity, early blood losses, or hemolysis. In contrast, iron deficiency in older infants and toddlers is usually a result of dietary deficiency, most commonly a result of excessive cow’s milk intake. Cow’s milk is a poor source of iron, with only 0.5-1 mg/L of iron and with only 10% of the iron bioavailable. Furthermore, excessive intake of cow’s milk is associated with decreased intake of other, more iron-rich, foods. Cow’s milk also frequently causes mucosal irritation in the GI tract, leading to chronic lowgrade blood loss. As iron deficiency develops slowly, over months to years, even severe anemia is relatively well tolerated by children with few symptoms. After correction of the iron deficiency, however, parents often note that children are less pale, have more energy, and are less “cranky.” Management of diet-associated iron deficiency involves decreasing or eliminating cow’s milk intake and increasing the intake of other iron-rich foods such as meats and leafy green vegetables, in addition to added oral iron supplements as needed.

Children with acute leukemias usually present with other cytopenias in addition to anemia and are commonly symptomatic from their cytopenias, with fevers, fatigue, petechiae, and bleeding. Anemia of chronic disease occurs in patients with a history of chronic inflammation, such as those with collagen vascular diseases, chronic infections (particularly osteomyelitis and tuberculosis), or renal insufficiency. The anemia of chronic disease is generally mild and of slow onset and is secondary to poor utilization of iron stores and suboptimal bone marrow responsiveness to erythropoietin. Management involves treatment of the underlying disease, as additional iron will not be used by the bone marrow or be effective in raising the hemoglobin level. Lead poisoning can be associated with microcytic anemia and is also frequently associated with iron deficiency. The latter results in increased lead absorption and toxicity. Anemia because of lead poisoning is usually a late finding and, fortunately, is rare in modern times because of the removal of lead from previously common sources such as paint and gasoline.

2.
(A)
The complete blood count with peripheral smear is the single most useful diagnostic test for iron deficiency. The complete blood count not only details the magnitude of anemia but also reports on red blood cell features, including the MCV and RDW, which will help to differentiate the anemia of iron deficiency (characterized by a low MCV and high RDW) from anemia because of thalassemia (characterized by a low MCV with a normal RDW). Furthermore, the peripheral smear will demonstrate the characteristic microcytosis with hypochromia and poikilocytosis of iron deficiency. The serum ferritin level is normally decreased with iron deficiency but can be falsely normal or high with any concurrent systemic inflammation. A hemoglobin electrophoresis would be useful to diagnose beta-thalassemia or other hemoglobinopathies but is not helpful in the diagnosis of iron deficiency. Electrophoresis in patients with thalassemia can be falsely normal in the presence of iron deficiency. The Coombs tests look for antibodies to red blood cells in the patient’s serum (indirect) or bound directly to the patient’s red blood cells (direct), and are useful to diagnose autoimmune hemolytic anemias but would not be useful in this case.

3.
(B)
Folate deficiency is a cause of macrocytic anemia and is also associated with hypersegmentation of neutrophils on the peripheral smear. The differential diagnosis of microcytic anemia in children includes lead poisoning, alpha- and beta-thalassemia, iron deficiency, anemia of chronic disease, and sideroblastic anemia. Iron deficiency is by far the most common, occurring in up to 10% of children in the United States. The anemia of chronic disease is also common but can be normocytic in more than half of the cases. Anemias due to hemoglobinopathies such as sickle cell disease, red blood cell enzyme defects or structural defects, and autoimmune hemolytic anemias are all generally normocytic. Macrocytic anemias can result from folate deficiency, vitamin B
₁₂
deficiency, or myelodysplastic or aplastic anemias.

4.
(A)
The average adult man has approximately 5 g of total body iron, and most (60-80%) of the body’s total iron is bound to erythrocyte hemoglobin. Approximately 10-30% of the total body iron stores are located in the reticuloendothelial cells of the liver and spleen. The heart and liver have only minimal amounts of iron under normal conditions, but they can contain large amounts of iron in states of iron overload. Only 0.1% of the total body iron stores can be found in the plasma, bound to transferrin. Only 1 mg of the total body iron is lost each day through sloughed skin and enteric mucosal cells and therefore must be replaced through the diet. The human body, unfortunately, has no other mechanism for selective iron excretion.

5.
(A)
Dietary iron is generally absorbed in the duodenum, and the absorption is regulated both in the form of the dietary iron as well as by the local intestinal environment. At neutral pH, iron is primarily in the ferric (Fe+3) form, which is poorly absorbed. In the stomach and duodenum, the acidic pH converts iron to the ferrous (Fe+2) form, which is more readily absorbed. Furthermore, iron found in heme moieties (from meat sources) is more readily absorbed compared with free elemental iron. Ascorbic acid and citric acid increase the absorption of iron from the intestine by reducing the iron from the ferric to the ferrous state. Phytates (found in soy-based formulas) and phosphates (found in cow’s milk) both bind to free iron in the GI tract and inhibit its absorption. Bicarbonate increases the gastric pH, which also inhibits conversion of iron to its ferrous form and reduces its absorption.

6.
(D)
The activity level of adolescents is unrelated to their iron stores. However, any cause of chronic blood loss, such as heavy menstrual bleeding, or any period of increased physiologic iron demand, such as pregnancy or growth spurts, can lead to iron deficiency. Dietary causes of iron deficiency are extremely rare in adolescents but can occur with unusual dietary patterns, such as strict vegetarianism or anorexia nervosa.

7.
(C)
Cardiomyopathy is generally not a complication of iron deficiency, although children with severe long-standing anemia of any etiology can have cardiac dysfunction as a result of excessive workload. Geophagia, a form of pica, along with cognitive delays, delayed growth, and irritability, are all associated with iron deficiency. The cognitive delays, unfortunately, may not be totally reversible with correction of the iron deficiency. Iron deficiency has also been associated with breath-holding spells, febrile seizures, proteinlosing enteropathy (because of the loss of enteric mucosal cells), and, rarely, thromboembolic strokes hypothesized to be secondary to a decrease in red blood cell membrane fluidity and flexibility that occurs with iron deficiency.

8.
(A)
The presence of iron deficiency is associated with a variety of laboratory abnormalities, including abnormalities in the blood count and abnormalities of other serum proteins. The features of iron deficiency in the complete blood count include a low MCV, an increased RDW, and associated hypochromia and poikilocytosis. Laboratory values consistent with iron deficiency include decreased ferritin, increased TIBC, decreased serum transferrin saturation, increased free erythrocyte protoporphyrin, and decreased serum iron. Anemia of chronic disease, by comparison, is characterized by a decreased TIBC and a normal serum ferritin level, whereas beta-thalassemia is generally associated with normal to increased serum iron, normal TIBC, and normal to increased serum ferritin levels.

9.
(D)
Folic acid therapy is not indicated for treatment of iron deficiency except in those cases of combined iron and folate deficiency, such as with severe malnutrition. Although oral ferrous sulfate at 3-6 mg/kg of elemental iron per day is the usual first option for treatment, intravenous iron therapy is an option for those patients with extremely low iron stores or those who would not absorb or tolerate oral iron. Red blood cell transfusions can be used for patients with very severe anemia, and the iron from the transfused red blood cells can then be recycled by the body for future red blood cell production as well. Responses to treatment for iron deficiency anemia are generally rapid, with an increase in reticulocytes occurring within 7 days and increased hemoglobin levels by 1 month.

Iron deficiency anemia develops slowly over time and progresses through several stages. Initially, depletion of the total body iron stores results in low serum ferritin levels but unchanged hemoglobin and serum iron levels. Upon complete iron store depletion, the serum iron level drops, associated with an increase in the serum TIBC. Further loss of iron then results in “iron deficiency anemia,” with development of the microcytic, hypochromic anemia characteristic of iron deficiency. Repletion of iron, either by oral, intravenous, or transfusion therapy, initially replaces the red blood cell iron, with normalization of the hemoglobin level and red blood cell MCV. However, in the absence of further aggressive iron repletion, the serum iron and ferritin levels remain low, and the patient remains in a state of “iron-limited erythropoiesis.” Therefore, it is crucial that iron replacement therapy be continued for several months after the normalization of the red blood cell parameters to ensure adequate replacement of the total body iron stores.

10.
(A)
Thalassemias are blood disorders characterized by decreased alpha- or beta-globin chain production, and they have a wide spectrum of clinical symptoms based on the relative levels of the alpha- and betaglobin chains. beta-thalassemia is most commonly found in persons of Mediterranean, northeast African, Indian, Indonesian, and Southeast Asian descent. The gene frequency can be as high as 20% in these populations. In contrast, beta-thalassemia is extremely rare in populations from northern Europe and the far East (Korea, China, and Japan). Alphathalassemia can be found primarily in Mediterranean, West African, and southwestern Pacific populations, with a gene frequency of up to 70% in some southwestern Pacific populations. It is extremely rare in populations from Great Britain, Iceland, and Japan.