Hereditary poikilocytic anemia associated with the co-inheritance of two
alpha spectrin abnormalities
TA Iarocci, GM Wagner, N Mohandas, PA Lane and WC Mentzer
Department of Pediatrics, University of California, San Francisco.
This report describes a black family in which two distinct structural
defects of alpha spectrin were inherited singly and in combination. The
propositus, who has a poikilocytic hemolytic anemia that shares many of the
features of hereditary pyropoikilocytosis (HPP) or homozygous
elliptocytosis, is a compound heterozygote for both the spectrin alpha 1/65
and spectrin alpha 1/50a defects as demonstrated by electrophoretic
analysis of spectrin tryptic fragments. The spectrin alpha 1/65 defect
alone was found in his mother and sibling, while the spectrin alpha 1/50a
defect was present in the father and another sibling. The red cell spectrin
content was normal in all family members. The functional consequences of
inheritance of these two spectrin defects were compared with those found in
an unrelated patient with classic HPP who had the alpha 1/50a spectrin
defect and was spectrin deficient as well. Prolonged incubation at 37
degrees C resulted in striking budding, fragmentation, and sphering of
classic HPP red cells but only minimal changes in propositus cells. The
percentage of spectrin dimers was increased tenfold in classic HPP,
sevenfold in the propositus, and threefold in other family members.
Mechanical stability of erythrocyte ghosts, measured by ektacytometry, was
reduced severely in both classic HPP and in the propositus, but only
moderately in other family members. Thus, co-inheritance of two alpha
spectrin defects can result in a poikilocytic hemolytic anemia milder than
that usually found in HPP. The greater clinical severity of HPP may be a
consequence of the presence of spectrin deficiency, a finding absent in the
propositus.
Volume 71,
Issue 5,
pp. 1390-1396,
05/01/1988
Copyright © 1988 by The American Society of Hematology
