Double inheritance of an alpha I/65 spectrin variant in a child with
homozygous elliptocytosis
M Garbarz, MC Lecomte, D Dhermy, C Feo, I Chaveroche, H Gautero, O Bournier, C Picat, A Goepp and P Boivin
Hemolytic anemia with red cell fragmentation, poikilocytosis, and
elliptocytosis was discovered in a 6-week-old black infant. Both parents
and a brother of the propositus had compensated mild Hereditary
Elliptocytosis (HE). Elliptocytosis was prominent in the proband's father
with the presence of numerous rod-shaped cells whereas, in the proband's
mother, elliptocytosis was less marked and cells were less elongated than
in the father. The proband's red cells fragmented at 45 degrees C instead
of 49 degrees C for control cells. Both the parents' and brother's red
cells fragmented at 47 degrees C. The deformability of the proband's red
cells was markedly reduced when measured with the ektacytometer; the red
cells of both the proband's parent and brother exhibited an intermediate
decrease in red cell deformability. Spectrin self-association was defective
in the propositus as well as in his parents and brother. Limited tryptic
digestion of the proband's spectrin, followed by sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE), revealed a complete absence
of the normal 80,000 dalton alpha I domain and the presence of an abnormal
65,000 dalton peptide. Two-dimensional isoelectric focusing/SDS-PAGE of
limited tryptic digests of spectrin from both the proband's parents and
brother revealed a decrease in the normal 80,000 alpha I domain and the
presence of the 65,000 peptide variant. On the basis of biochemic studies
performed on the patients' spectrin, we concluded that the proband had
homozygous HE, having inherited the structural defect of spectrin present
in a heterozygous state in each of his parents. On a clinical and
morphologic level, homozygous HE imitates two other forms of congenital
hemolytic anemia associated with a spectrin self- association defect: HE
with pycnocytosis in infancy and Hereditary Pyropoikilocytosis. This report
emphasizes the importance of confronting clinical and rheological as well
as biochemical investigations in studying and discussing different
entities.
Volume 67,
Issue 6,
pp. 1661-1667,
06/01/1986
Copyright © 1986 by The American Society of Hematology
