Hereditary pyropoikilocytosis (HPP) is a red cell membrane disorder classified under the broad umbrella of hereditary elliptocytosis (HE). It is usually the most severe form of HE and is inherited in an autosomal recessive manner. HE results from alterations in RBC membrane cytoskeleton proteins: spectrin, ankyrin, pallidin, band 4.1, and band 3. Quantitative or qualitative deficiencies result in varying clinical syndromes. In general, mutations in the α gene are closer to the amino terminal, and those in the β spectrin gene are nearer the carboxyl terminal and affect the formation of tetramers. We describe a patient associated with a novel mutation in the β and α spectrin genes. A 19 year old black female with a lifelong history of anemia and jaundice that worsened since age 15 presented with history of early satiety of a few months duration. Neither parent had a history of a blood disorder; a maternal uncle had history of splenectomy in his thirties. Her pre-splenectomy labs showed a Hb of 4.8g/dl with a MCV of 62, RDW of 38.8, and chemistries consistent with non-immune hemolytic anemia. Imaging and clinical exam revealed a spleen of 19cms and bizarre red cell morphology including RBC fragmentation and microcytosis. Post splenectomy the patient is entirely asymptomatic with a Hb of 13.2 with pathologic exam of the spleen showing benign, enlarged, red pulp consistent with hypersplenism. Genomic DNA was extracted from peripheral blood. Sequencing of the β-spectrin exon 30 was undertaken at the MCG Sickle Cell Center that revealed a GCT → CCT mutation (Ala → Pro) in codon 2053. This mutation has been previously reported in the homozygous state in a young boy from Mali with HPP (β spectrin Kayes). Since we could not explain the relatively severe phenotype in this patient with heterozygous β spectrin Kayes, further molecular analyses was performed at Yale. This revealed a mutation in the α-spectrin exon 5; L207P, α spectrin St.Louis. This is the 2nd reported case of HPP due to compound heterozygosity for an α and β spectrin mutation and the first combination of α spectrin St. Louis and β spectrin Kayes.
Disclosure: No relevant conflicts of interest to declare.