Decreased Activity Level - Case 2-1: 15-Year-Old Girl
Decreased Activity Level - Case 2-1: 15-Year-Old Girl: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
I. History of Present Illness
A 15-year-old girl presented to the emergency department with a 3-month history
of increasing fatigue. She had gradually stopped participating in sports
because of dizziness and palpitations. Her decreased level of activity had
worsened to the point that as soon as she returned home from school in the
afternoon she went to bed and slept the rest of the day. She had had an
18-pound weight loss over the 3-month period. In addition, for the past 5 days
she had had a headache and occasional nonbloody, nonbilious emesis. For the
past 4 days she had also had mild upper abdominal pain. The remainder of her
history and review of systems were noncontributory.
II. Past Medical History
She was the product of a full-term delivery and had had no major medical
illnesses. She had not required any surgeries.
III. Physical Examination
T, 37.2°C; RR, 16/min; HR, 110 bpm; BP, 100/60 mm Hg
Weight and height, 25th percentile
On examination, she appeared pale and tired but was not toxic-appearing. She
answered questions appropriately. The head and neck examination revealed pale
conjunctiva. She did not have any papilledema. Her lungs were clear to
auscultation. Cardiac examination revealed tachycardia but no murmurs or other
abnormal heart sounds. Her abdomen was soft with normal bowel sounds. There was
no hepatosplenomegaly. Capillary refill was delayed at 3 seconds. Her
neurologic examination was normal. Of particular interest, her cranial nerve
examination and motor strength were normal.
IV. Diagnostic Studies
A complete blood count revealed a white blood cell (WBC) count of 2,100 cells/mm3, including 3% bands, 45% segmented neutrophils, and 51% lymphocytes. Hemoglobin
was 5.4 g/dL, and the platelet count was 173,000/mm
3. The mean corpuscular volume (MCV) was elevated at 98.7 fL.
V. Course of Illness
The patient was hospitalized for evaluation of her severe anemia. The peripheral
blood smear provided a clue to the diagnosis (Fig. 2-1).
Discussion: Case 2-1
I. Differential Diagnosis
This patient had a significant anemia. There are several categories of anemia.
The anemia could be caused by a nutritional deficit (e.g., iron, folic acid,
vitamin B
12). It could be caused by a hemoglobinopathy (e.g., sickle cell anemia,
thalassemia). The anemia could also be the result of a hemolytic process such
as hereditary spherocytosis or glucose-6-phosphate dehydrogenase deficiency.
Finally, the anemia could result from a hypoplastic or aplastic crisis.
When evaluating anemia, it is easiest to arrive at the correct diagnosis by
assessing the hematologic indices, specifically the MCV. If the MCV is low, the
anemia is a microcytic anemia and causes such as iron deficiency anemia, lead
poisoning, anemia of chronic disease, and thalassemias should be considered. If
the MCV is normal, chronic disease, hypoplastic or aplastic crisis, malignancy,
renal failure, acute hemorrhage, and hemolytic processes should be considered.
Finally, if the MCV is high, the megaloblastic anemias should be evaluated,
specifically folate deficiency and vitamin B
12 deficiency, as well as some of the aplastic anemias.
II. Diagnosis
This patient had a macrocytic anemia, as indicated by an elevated MCV of 98.7
fL. A hypersegmented neutrophil is located in the center of the peripheral
blood smear in Fig. 2-1. In the lower portion of the figure are several
megaloblasts with a loose-appearing nuclear chromatin. Also noted are numerous
misshapen mature erythrocytes, reflecting the mechanical fragility associated
with megaloblastic anemias. As the appropriate next step, serum levels of
folate and vitamin B
12 were measured. The folate level was 8.2 ng/mL (normal range, 2 to 20 ng/mL).
The vitamin B
12 level was less than 100 pg/mL (normal range, 200 to 1,100 pg/mL). On further
questioning, the patient stated that she had been a strict vegetarian for the
past 2 years and had eaten no meat or animal-based products. Additionally, she
did not take vitamin supplements and did not attempt to eat non-meat-based
foods containing vitamin B
12, such as fortified cereal and fortified meat analogs (e.g., wheat gluten, soy
products).
The diagnosis is dietary vitamin B12 deficiency.
III. Incidence and Epidemiology
To be absorbed, dietary vitamin B12 must combine with a glycoprotein (intrinsic factor), which is secreted from the
gastric fundus. The vitamin B
12–intrinsic factor complex then is absorbed at the terminal ileum via specific
receptor mechanisms. Vitamin B
12 is present in many foods, and a pure dietary deficiency is rare. However, it
may be seen in patients who do not eat any milk, eggs, or animal products
(vegans). Vitamin B
12 deficiency can also result from lack of secretion of intrinsic factor in the
stomach. When the cause of the lack of intrinsic factor is chronic atrophic
gastritis, this condition is referred to as pernicious anemia. Other causes of
vitamin B
12 deficiency include surgical resection of the terminal ileum, regional enteritis
of the terminal ileum, overgrowth of intestinal bacteria, disruption of the B
12–intrinsic factor complex, abnormalities or absence of the receptor site in the
terminal ileum, and inborn errors in the metabolism of vitamin B
12.
IV. Clinical Presentation
Vitamin B12 plays an important role as a cofactor for two metabolic reactions: methylation
of homocysteine to methionine and conversion of methylmalonyl coenzyme A (CoA)
to succinyl CoA. Vitamin B
12 deficiency leads to accumulation of these precursors. Methionine is an
important step in the synthesis of DNA. In individuals with vitamin B
12 deficiency, RNA and cytoplasmic components are produced normally, and red blood
cell (RBC) production in the bone marrow yields large cells and, hence, a
macrocytic anemia. Methionine is also converted to S-adenosylmethionine, which
is used in methylation reactions in the CNS; therefore, CNS effects are seen
with vitamin B
12 deficiency. Neurologic manifestations in children include abnormalities such as
paresthesias, loss of developmental milestones, hypotonia, seizures, dementia,
and depression. The neurologic changes are not always reversible.
V. Diagnostic Approach
Complete blood count and folic acid and vitamin B12 levels. The term megaloblastic anemia refers to a macrocytic anemia usually accompanied by a mild leukopenia or
thrombocytopenia. The presence of a macrocytic anemia with normal folic acid
levels and low vitamin B
12 levels is diagnostic for most vitamin B12 deficiencies. However, reliance on abnormal hemoglobin may miss up to 30% of
adult cases of vitamin B
12 deficiency. On peripheral blood smear, there are numerous schistocytes and
misshapen mature RBCs due to the increased mechanical RBC fragility associated
with this condition. Erythroid precursors have loose-appearing chromatin,
giving them a characteristic appearance. Hypersegmented or multilobar
neutrophils may also be noted. The appearance of at least one neutrophil with
more than six lobes, or more than five neutrophils with more than five lobes,
is considered significant. In vitamin B
12 deficiency, serum levels of homocysteine and methylmalonyl CoA may be elevated,
assisting in the diagnosis. Levels of methylmalonic acid (MMA), a precursor to
methylmalonyl CoA, may be elevated as well.
Other studies. After the diagnosis of vitamin B12 deficiency has been made, further studies can be performed to identify the
cause. Specifically, a comprehensive dietary assessment, evaluation for
parasitic infections, a Schilling test (which measures the ability to absorb
orally ingested vitamin B
12), amino acid analysis, measurement of the unsaturated B12 binding capacity and transcobalamin II levels, genetic evaluation, and
measurement of antibodies to parietal cells and intrinsic factor may be
performed. Subspecialty consultation is often required to assist with the
diagnosis.
VI. Treatment
Treatment of vitamin B12 deficiency depends on the cause. Frequently, vitamin B12 administration is necessary. If the anemia is severe, treatment should be
instituted slowly and in a monitored environment. For malabsorptive causes,
long-term treatment is indicated. The recommended treatment is monthly
injections of 100
µg of vitamin B12. Monitoring of the clinical response and laboratory values enables the
clinician to titrate treatment to the patient
's response. It is not known whether folic acid therapy in patients who have
vitamin B
12 deficiency will worsen the neurologic symptoms of the vitamin B12 deficiency; it may mask the hematologic symptoms of the megaloblastic anemia.
In this case, the patient received a vitamin B
12 injection and then began oral multivitamin and vitamin B12 supplementation. She also received nutritional counseling to help her create a
nutritionally balanced vegan diet.
VII. References
1. O'Grady LF. The megaloblastic anemias. In: Keopke JA, ed. Laboratory hematology. New York: Churchill Livingstone, 1984:71–83.
2. Rasmussen SA, Fernhoff PM, Scanlon KS. Vitamin B12 deficiency in children and adolescents. J Pediatr 2001;138:10–17.
3. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency: a guide for the primary care physician. Arch Intern Med 1999;159:1289–1298.
4. Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med 1997;337:1441–1448.
5. Whitehead VM, Rosenblatt DS, Cooper BA. Megaloblastic anemia. In: Nathan DG,
Orkin SA, eds.
Nathan and Oski's hematology of infancy and childhood, 5th ed. Philadelphia: WB Saunders, 1998:385–422.
Pictures
Book Source Details
- Book Title: Pediatric Complaints and Diagnostic Dilemmas
- Author(s): Samir S Shah MD; Stephen Ludwig MD
- Year of Publication: 2003
- Copyright Details: Pediatric Complaints and Diagnostic Dilemmas, Copyright © 2003 Lippincott Williams & Wilkins.
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