Hereditary pyropoikilocytosis was originally described by Zarkowsky et al. (1975) as a distinct hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.
HPP is a subset of hereditary elliptocytosis (see 611804) ... Hereditary pyropoikilocytosis was originally described by Zarkowsky et al. (1975) as a distinct hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells. HPP is a subset of hereditary elliptocytosis (see 611804) due to homozygous or compound heterozygous mutations in spectrin leading to severe disruption of spectrin self-association (review by An and Mohandas, 2008).
Liu et al. (1981) studied 2 patients from unrelated black families. Both had a history of hemolytic anemia since birth (Palek et al., 1981). Spectrin from the abnormal cells has an increased susceptibility to thermal denaturation (Chang et ... Liu et al. (1981) studied 2 patients from unrelated black families. Both had a history of hemolytic anemia since birth (Palek et al., 1981). Spectrin from the abnormal cells has an increased susceptibility to thermal denaturation (Chang et al., 1979). Liu et al. (1981) concluded that self-association of spectrin dimers into tetramers is defective, thus accounting for the instability of red cell membrane skeletons. The asymptomatic mothers, presumed heterozygotes, showed a mild but reproducible increase of spectrin dimers in 0 degree C extracts and a defective reassociation of spectrin dimers to tetramers both in solution and in the membrane. The mothers showed normal red cell morphology and thermal stability. Mallouh et al. (1984) reported Saudi brother and sister with HPP. Both parents and 8 sibs had normal red cells; 3 sibs had elliptocytosis on peripheral blood smears. Lecomte et al. (1987) described a Caucasian kindred in which a woman and 2 of her maternal uncles had HPP with severe hemolytic anemia, whereas her mother and daughter had mild hereditary elliptocytosis. The proposita's father was clinically and hematologically normal and had no abnormality of red cell membranes. A defect in alpha-spectrin was found in all 5 individuals. The reason for the phenotypic differences was not clear.
Gallagher et al. (1992) demonstrated that one of the original HPP probands reported by Zarkowsky et al. (1975) had a substitution of proline for leucine at position 207 of the alpha-spectrin chain (L207P; 182860.0016). By analysis of reticulocyte ... Gallagher et al. (1992) demonstrated that one of the original HPP probands reported by Zarkowsky et al. (1975) had a substitution of proline for leucine at position 207 of the alpha-spectrin chain (L207P; 182860.0016). By analysis of reticulocyte alpha-spectrin cDNA from one of the HPP patients reported by Zarkowsky et al. (1975), Costa et al. (2005) demonstrated that the non-L207P allele had a G-to-A transition at position +5 of the donor splice site of intron 22 of the SPTA1 gene (182860.0024). In affected members of 2 families segregating HPP, Sahr et al. (1993) identified homozygosity for a mutation in the SPTB gene (182870.0008).