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376 Part IV Disorders of Hematopoietic Cell Development

Hematologic Features in Diamond-Blackfan Anemia at 31% and 11% of patients, respectively, either at presentation or at
TABLE Diagnosis Based on Data on 21 Toronto Cases and on follow-up. Progression of the single-lineage erythroid deficiency of
29.6 41 Cases From the Canadian Inherited Marrow Failure DBA into pancytopenia and severe aplastic anemia is rare but occurs.
Registry Of 36 deaths reported to the American DBA Registry, one died from
severe aplastic anemia.
Hematologic Parameters Laboratory Findings
Mean hemoglobin value (range) Erythrocyte Findings. Erythrocytes in DBA express a number of
Newborns younger than 2 months of 6.5 g/dL (1.7–9.1 g/dL) fetal characteristics. The level of HbF is increased persistently even
age during remission. It remains at a level of about 10% after the age of
Children 2 months of age or older 4.0 g/dL (1.8–7.4 g/dL) 6 months and has a heterogeneous distribution in RBCs. The HbF
has a specifically fetal amino-acid profile with a high glycine-to-alanine
High MCV for age after the age of 1 year 87% ratio (G-γ:A-γ). Similarly, the i antigen, which normally disappears
Low reticulocyte for the degree of anemia 100% (usually markedly from the erythrocyte surface by 1 year of age, is expressed at near fetal
decreased to <1%) levels in older patients with DBA.
Increased HbF for age after 1 year of age 100% The precise cause of this fetal-like erythropoiesis is unclear. It is
clearly distinct from the fetal erythropoiesis implicated in various
RBC adenosine deaminase activity 77% types of leukemia, notably in juvenile myelomonocytic leukemia in
RBC i antigen Expression increased which the fetal RBCs presumably arise from the leukemic clone. The
beyond first year of life situation in DBA may be analogous to that in other forms of BM
RBC enzymes Fetal pattern failure and in the hematologic recovery phase after BMT. In all of
these conditions, the fetal (or “stress”) erythropoiesis may represent
Neutropenia 31%
an accelerated recapitulation of RBC ontogeny in the face of an
Thrombocytopenia 11% increased demand for new RBCs in peripheral blood.
BM cellularity Normal or increased in Red blood cell enzymes often display an abnormal pattern of
90%; mildly reduced activity that reflects a fetal expression pattern of RBC glycolytic and
in 10% hexose monophosphate shunt enzyme activities. Enzymes, such as
enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphofructo-
BM erythropoiesis Markedly reduced/absent kinase, and glutathione peroxidase, have increased activity in patients
erythroid precursors in with DBA compared with those in normal children and adults and
>90% of cases in patients with transient erythroblastopenia of childhood (TEC).
BM myeloid and megakaryocytic lineages Normal in 100% of the For some enzymes, this increased activity is comparable to cord blood
cases RBCs. In apparent contradiction, carbonic anhydrase isoenzyme B,
BM, Bone marrow; HbF, fetal hemoglobin; MCV, mean corpuscular volume; which is not normally present in fetal RBCs, was detected in hemo-
RBC, red blood cell. lysates from three patients with DBA. Also, the RBCs of two of the
three patients had adult hexokinase isoenzyme distribution by iso-
electric focusing.
Abnormalities in purine and pyrimidine metabolism are
reflected by increased activity of RBC adenosine deaminase (ADA)
in 60% to 90% of patients with DBA. Also, increased orotidine
decarboxylase (ODC) activity is seen in some patients. ADA activity
is raised in DBA erythrocytes but not in cord blood RBCs from
normal newborns or from patients with any of several hematologic
conditions associated with “stress” erythropoiesis. Thus this enzymatic
abnormality cannot be simply attributable to a “reversion” to fetal
erythropoiesis. Raised ADA activity may also be detected in some
hemolytic anemias and acute leukemias, which limits the utility of
this assay as a specific diagnostic marker for DBA. However, increased
ADA activity does appear to be useful in differentiating DBA from
acquired pure cell anemias such as TEC and for epidemiologic
testing of DBA pedigrees to identify family members with a mild
phenotype.
Miscellaneous Findings. Serum levels of various factors involved
in RBC production, such as erythropoietin, iron, vitamin B 12 , and
folate, are appropriately elevated in DBA. These findings are compat-
ible with any form of chronic hypoplastic anemia. Riboflavin levels
Fig. 29.10 HIGH-POWER VIEW OF A BONE MARROW ASPIRATE are normal in the serum but not in the erythrocytes. This observation
FROM A NEWLY DIAGNOSED INFANT WITH DIAMOND- initially aroused interest because experimental riboflavin deficiency
BLACKFAN ANEMIA. The findings are active granulopoiesis; normal may be corrected by corticosteroids similar to DBA. However,
lymphoid activity for age; and an isolated pronormoblast (arrow) with total administration of large doses of riboflavin to several DBA patients
absence of early-, intermediate-, and late-stage nucleated red blood cells. did not result in a hematopoietic response. RBC serology is usually
(Photomicrograph prepared by Dr. Mohamed Abdelhaleem, Toronto.) unremarkable at the time of diagnosis, but alloantibodies are fre-
quently detected in chronically transfused patients.

Imaging Studies. Imaging studies are frequently informative and
cases, proerythroblasts may be present in normal numbers, with or assist in establishing a diagnosis. Skeletal radiography may define
without a maturation arrest. White blood cell counts and platelet abnormalities suspected from physical examination, such as hypo-
counts are usually normal at diagnosis, but platelets may be increased plastic, absent, or extra phalanges. Ultrasound of the abdomen may
with normal function. Among DBA patients enrolled in the CIMFR reveal malformations such as of the urogenital system. Echocardiog-
mild to moderate neutropenia and thrombocytopenia occurred in raphy may reveal undiagnosed cardiac defects.