Pallor - Case 10-1: 3-Week-Old Boy
Pallor - Case 10-1: 3-Week-Old Boy: Excerpt from Pediatric Complaints and Diagnostic Dilemmas
I. History of Present Illness
A 3-week-old twin B Caucasian male infant presented to an outpatient clinic for
evaluation of anemia. He was noted in the nursery to be pale and had a
hemoglobin of 12.3 g/dL and a mean corpuscular volume (MCV) of 120 fL. The
hemoglobin measurement repeated at 2 weeks of age was 8.1 g/dL with a
reticulocyte count of 1.2%. He had initial problems with weight gain that
improved after the mother started to pump breast milk and to feed the baby with
a bottle. He was described as usually sleepy, including falling asleep during
feeds. He had no vomiting, diarrhea, fever, or cough. He had normal
gold-colored bowel movements. There had been no change in urine color. There
was no rash.
II. Past Medical History
The infant was born at 38 weeks' gestational age after in vitro fertilization. The pregnancy was complicated by maternal anemia. The mother's blood type was O-positive. The mother did not receive any medications during
pregnancy except for prenatal vitamins. The infant was delivered vaginally. He
had a transverse lie and was delivered vertex after external manipulation. The
birth weight was 2,470 grams. His twin (twin A) weighed 2,900 g. On the first
day of life, the infant was noted to have a swollen right upper leg with
significant bruising. The initial radiograph was normal, but a subsequent film
showed evidence of a healing fracture that was presumably related to birth
trauma. There was no history of jaundice in the newborn nursery.
The family history was remarkable for the mother's anemia which did not require specific treatment. The maternal grandmother also
had a history of anemia. Both the maternal grandmother and an aunt had required
cholecystectomy for gallstones. The infant received a multivitamin with iron.
He did not have any known allergies. He received a diet of breast milk with
occasional cow
's milk supplementation.
III. Physical Examination
T, 36.7°C; RR, 46 to 66/min; HR, 166 to 230 bpm; BP, 70/37 mm Hg
Weight, 3.1 kg (25th percentile); height, 50 cm (50th percentile); head
circumference, 36 cm (approximately 75th percentile)
On examination, the infant awakened easily and cried. He was remarkably
pale-appearing. The anterior fontanel was open and flat. The conjunctivae were
pale. The sclerae were anicteric. Mucous membranes were moist. The clavicles
were intact. The infant was tachypneic, but the lungs were clear to
auscultation. On cardiac examination, normal first and second heart sounds (S1
and S2, respectively) were heard. A III/VI systolic murmur was best appreciated
at the left upper sternal border. There were no gallops or rubs. No murmurs
were heard along the back. The liver edge was just palpable, but the spleen was
not palpable. The area of known extremity fracture had minimal edema but no
tenderness. There was some widening of the right distal femur compared with the
left. The remainder of the examination was normal.
IV. Diagnostic Studies
Complete blood count revealed the following: 11,300 white blood cells (WBCs)/mm3 (1% metamyelocytes, 43% segmented neutrophils, 34% lymphocytes, and 19%
monocytes); hemoglobin, 3.9 g/dL; 430,000 platelets/mm
3; MCV, 117 fL; RBC distribution width (RDW), 17; and reticulocyte count, 0.3%.
The peripheral blood smear revealed a few small spherocytes but no
schistocytes, burr cells, or target cells.
V. Course of Illness
The child was admitted for evaluation of anemia.
Discussion: Case 10-1
I. Differential Diagnosis
This male child presented with pallor at a young age. There was no history of
jaundice, which lessened the likelihood of a hemolytic anemia. There was no
issue of dietary causes because of the baby
's young age. No chronic illness was apparent, and there was no history of blood
loss. Therefore, the focus shifted to a congenital defect in RBC production.
There was a remarkable drop in the hemoglobin and a very poor bone marrow
response as far as reticulocyte production. The WBC and platelet concentrations
were normal. The anemia was macrocytic. The sum of these findings indicated a
defect of RBC production. There was also the physical examination finding of a
possible skeletal anomaly at the distal right femur.
RBC aplasia may be congenital or acquired. Most of the acquired forms occur in
adults, but some may be seen in adolescent patients. In childhood, the major
causes are Diamond-Blackfan anemia, transient erythroblastopenia of childhood,
and acquired aplasia of RBCs associated with chronic hemolysis. The aplastic
crisis of a sickle cell disease patient is an example of the latter.
In this case, there was no evidence of acute or chronic hemolysis. The patient
was too young to be considered for transient erythroblastopenia of childhood.
Another possible cause to be considered was Fanconi anemia, an autosomal
recessive disorder associated with aplastic anemia, short stature, skeletal
defects, pigmentation changes, and other abnormalities. Some cases of Fanconi
anemia are diagnosed in the first year of life. The anemia involves all cell
lines; bone marrow analysis and genetic studies establish the diagnosis. In
this case, there was only RBC involvement, and hence Diamond-Blackfan anemia
was the most plausible diagnosis.
II. Diagnosis
The infant was admitted with the diagnosis of anemia secondary to a
hypoproductive state. He was believed to have symptomatic anemia with
difficulty feeding. He was transfused with a total of 15 mL/kg of packed RBCs
administered in three separate aliquots. He underwent bone marrow aspiration,
which revealed absence of RBC precursors with normal granulocyte precursors, a
finding consistent with Diamond-Blackfan anemia. After the packed RBC
transfusion, he had a hemoglobin concentration of 8.7 g/dL. He was more active
and was in no respiratory distress. Corticosteroids were started at 2 mg/kg per
day, and an additional 5 mL/kg of packed RBCs was given before his discharge
home.
The final diagnosis was Diamond-Blackfan anemia. It is one of the pure RBC aplasias.
III. Incidence and Epidemiology
The precise incidence of Diamond-Blackfan anemia is not known. For all the RBC
aplasias, it is estimated that there are 300 to 1,000 new cases annually in the
United States. Diamond-Blackfan anemia occurs primarily in infancy. In some
studies, 10% of patients are anemic at birth, 25% by 1 month, 50% by 3 months,
and 70% by 1 year. This anemia is seen in all ethnic groups, but primarily in
Caucasians. There is no gender predominance.
IV. Clinical Presentation
Pallor caused by anemia in the early months of life characterizes this form of
anemia. About one third of patients have an associated finding. There are many
associated anomalies, including characteristic facies, thumb anomalies, short
stature, eye abnormalities including glaucoma, renal anomalies, hypogonads,
skeletal anomalies, congenital heart disease, and mental retardation. There is
a wide range of involvement. The current median survival rate is 45 years. Some
patients progress to full aplastic anemia, and about 5% develop leukemia or
myelodysplasia.
V. Diagnostic Approach
Complete blood count and peripheral blood smear. The mean hemoglobin level at diagnosis for all patients with Diamond-Blackfan
anemia is 7 g/dL. Infants diagnosed in the first 4 months of life typically
have hemoglobin levels of 4 g/dL at presentation. The reticulocyte count is
decreased or zero. The peripheral blood smear reveals macrocytes, anisocytosis,
and teardrop cells. The WBC count is normal in most patients, but in 20% it is
less than 5,000/mm
3.
Bone marrow aspiration. Bone marrow aspirates and biopsies show normal cellularity, myeloid cells, and
megakaryocytes. Approximately 90% of patients have erythroid hypoplasia or
aplasia. The remaining 10% of patients have either normal erythroblast number
and maturation or erythroid hyperplasia with maturation arrest. Despite the
variable marrow findings, all patients have reticulocytopenia, indicating some
form of ineffective erythropoiesis and delayed precursor maturation.
Other studies. Serum iron, ferritin, folate, vitamin B12, and erythropoietin are all elevated. In most cases there is an increase in RBC
adenosine deaminase (ADA). Genetic studies have shown one site on chromosome
19, and other gene defects have also been associated.
VI. Treatment
The treatment includes use of corticosteroids. The currently recommended dose is
2 mg/kg per day of prednisone, given in three or four divided doses.
Reticulocytes appear within 1 to 2 weeks, but the rise in hemoglobin is delayed
for several more weeks. Once the hemoglobin level reaches 10 g/dL, the steroid
dose is gradually tapered until the patient is receiving a single daily dose
that adequately maintains appropriate hemoglobin levels. Response followed by
steroid dependence is seen in 60% of patients. Approximately one fifth of the
steroid-responsive patients may ultimately be maintained without steroids.
Approximately 30% to 40% of patients have poor or no response to steroids and
require chronic transfusion therapy to maintain normal hemoglobin. These
children require leukocyte-depleted packed RBC transfusions every 3 to 6 weeks,
with the goal of keeping the hemoglobin level higher than 6 g/dL. Concurrent
chelation of iron with subcutaneously administered desferrioxamine may decrease
some chronic transfusion-related complications. Complications of chronic
transfusion therapy are similar to those seen with other conditions that employ
this modality (e.g., thalassemia). Bone marrow transplantation has been
successful for some patients.
Median survival time is 43 years, but approximately 13% of patients die within
the first 6 years of life. Deaths occur from complications of iron overload,
pneumonia, sepsis, and occasionally transplant-related complications, leukemia,
and pulmonary emboli.
VII. References
1. Alter BP. Inherited bone marrow failure syndromes. In: Nathan DG, Orkin SH,
Ginsburg D, et al., eds.
Nathan and Oski's hematology of infancy and childhood, 6th ed. Philadelphia: WB Saunders, 2003:280–365.
2. Ball SE, McGuckin CP, Jenkins G, et al. Diamond-Blackfan anaemia in the UK:
analysis of 80 cases from a 20 year birth cohort.
Br J Haematol 1996;94:645–653.
3. Willing TN, Draptchinskaia N, Dianzani I, et al. Mutations in ribosomal
protein S19 gene and Diamond-Blackfan anaemia: wide variations in phenotypic
expression.
Blood 1999;94:4294–4306.
4. Willing TN, Gazda H, Sieff CA. Diamond-Blackfan anaemia. Curr Opin Haematol 2000;7:85–94.
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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