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The Spectrum of SPTA1-Associated Hereditary Spherocytosis.

Publication ,  Conference
Chonat, S; Risinger, M; Sakthivel, H; Niss, O; Rothman, JA; Hsieh, L; Chou, ST; Kwiatkowski, JL; Khandros, E; Gorman, MF; Wells, DT; Seu, KG ...
Published in: Front Physiol
2019

Hereditary spherocytosis (HS) is the most common red blood cell (RBC) membrane disorder causing hereditary hemolytic anemia. Patients with HS have defects in the genes coding for ankyrin (ANK1), band 3 (SLC4A1), protein 4.2 (EPB42), and α (SPTA1) or β-spectrin (SPTB). Severe recessive HS is most commonly due to biallelic SPTA1 mutations. α-spectrin is produced in excess in normal erythroid cells, therefore SPTA1-associated HS ensues with mutations causing significant decrease of normal protein expression from both alleles. In this study, we systematically compared genetic, rheological, and protein expression data to the varying clinical presentation in eleven patients with SPTA1-associated HS. The phenotype of HS in this group of patients ranged from moderately severe to severe transfusion-dependent anemia and up to hydrops fetalis which is typically fatal if transfusions are not initiated before term delivery. The pathogenicity of the mutations could be corroborated by reduced SPTA1 mRNA expression in the patients' reticulocytes. The disease severity correlated to the level of α-spectrin protein in their RBC cytoskeleton but was also affected by other factors. Patients carrying the low expression αLEPRA allele in trans to a null SPTA1 mutation were not all transfusion dependent and their anemia improved or resolved with partial or total splenectomy, respectively. In contrast, patients with near-complete or complete α-spectrin deficiency have a history of having been salvaged from fatal hydrops fetalis, either because they were born prematurely and started transfusions early or because they had intrauterine transfusions. They have suboptimal reticulocytosis or reticulocytopenia and remain transfusion dependent even after splenectomy; these patients require either lifetime transfusions and iron chelation or stem cell transplant. Comprehensive genetic and phenotypic evaluation is critical to provide accurate diagnosis in patients with SPTA1-associated HS and guide toward appropriate management.

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Published In

Front Physiol

DOI

ISSN

1664-042X

Publication Date

2019

Volume

10

Start / End Page

815

Location

Switzerland

Related Subject Headings

  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1701 Psychology
  • 1116 Medical Physiology
  • 0606 Physiology
 

Citation

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MLA
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Chonat, S., Risinger, M., Sakthivel, H., Niss, O., Rothman, J. A., Hsieh, L., … Kalfa, T. A. (2019). The Spectrum of SPTA1-Associated Hereditary Spherocytosis. In Front Physiol (Vol. 10, p. 815). Switzerland. https://doi.org/10.3389/fphys.2019.00815
Chonat, Satheesh, Mary Risinger, Haripriya Sakthivel, Omar Niss, Jennifer A. Rothman, Loan Hsieh, Stella T. Chou, et al. “The Spectrum of SPTA1-Associated Hereditary Spherocytosis.” In Front Physiol, 10:815, 2019. https://doi.org/10.3389/fphys.2019.00815.
Chonat S, Risinger M, Sakthivel H, Niss O, Rothman JA, Hsieh L, et al. The Spectrum of SPTA1-Associated Hereditary Spherocytosis. In: Front Physiol. 2019. p. 815.
Chonat, Satheesh, et al. “The Spectrum of SPTA1-Associated Hereditary Spherocytosis.Front Physiol, vol. 10, 2019, p. 815. Pubmed, doi:10.3389/fphys.2019.00815.
Chonat S, Risinger M, Sakthivel H, Niss O, Rothman JA, Hsieh L, Chou ST, Kwiatkowski JL, Khandros E, Gorman MF, Wells DT, Maghathe T, Dagaonkar N, Seu KG, Zhang K, Zhang W, Kalfa TA. The Spectrum of SPTA1-Associated Hereditary Spherocytosis. Front Physiol. 2019. p. 815.

Published In

Front Physiol

DOI

ISSN

1664-042X

Publication Date

2019

Volume

10

Start / End Page

815

Location

Switzerland

Related Subject Headings

  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1701 Psychology
  • 1116 Medical Physiology
  • 0606 Physiology