Inherited hemolytic anemia (IHA) cases previously undiagnosed have now been identified thanks to next-generation sequencing. When 21 unrelated Thai pediatric patients with non-thalassemic IHA presented with hydrops fetalis and/or became transfusion-dependent for a year or longer or for the rest of their lives, researchers used whole-exome sequencing to explore the molecular diagnostic spectrum.

Three, 12, and 6 individuals had prenatal, first-month, and fifth-year asymptomatic periods of anemia. The most often mutated gene (4 reported, 3 unique) identified from all patients’ molecular diagnoses was SPTB, which was present in 31 of 42 examined alleles. ANK1 (3 new mutations) and KLF1 were the other 2 altered genes found (2 reported). The bulk (90%) of mutant SPTB alleles were caused by four recurrent mutations in exon 29/30, which were biallelicly inherited and caused the most severe symptoms, including hydrops fetalis and lifelong transfusion dependence.

The duration of transfusion need was shortened by dominant ANK1 (n = 3), SPTB (n = 2), and biallelic class 2 KLF1 mutations (n = 1). The research showed that the most typical cause of severe non-thalassemic IHA in Thai patients was most likely mutant SPTB-producing red-cell membranopathy. It encouraged carrier screening in the populace to stop more seriously damaged babies.

Reference: onlinelibrary.wiley.com/doi/10.1111/bjh.18356