Screening of hereditary elliptocytosis caused by SPTB mutations and identification of its association with significant jaundice among Thai neonates.

Hereditary elliptocytosis (HE) caused by heterozygosity of three common SPTB mutations, namely SPTB Providence (c.6055T>C), SPTB Buffalo (c.6074T>G) and SPTB Chiang Mai (c.6224A>G), is the most prevalent form of red blood cell membranopathy in Thailand. Here, we explored the prevalence of the mutated SPTB-causing HE using molecular screening and demonstrated its impact on the development and severity of jaundice among Thai neonates. This cross-sectional study identified the three common SPTB mutations in cord blood samples from all neonates born at Ramathibodi Hospital from March to November 2024 using a recently developed robust, rapid molecular method. Clinical data related to neonatal jaundice were obtained from medical records and were analysed according to the presence of the SPTB mutations. A total of 1505 neonates with a mean (SD) gestational age of 37.5 (2.3) weeks were enrolled. Thirteen unrelated neonates were identified as having HE caused by the screened SPTB mutations, yielding a prevalence of 0.86%. The analyses revealed the mutated SPTB-causing HE as an independent risk factor for neonatal jaundice requiring phototherapy (risk ratio 5.01, 95% CI 2.56 to 9.79, p<0.001). The mean total bilirubin levels of neonates with the mutated SPTB-causing HE were significantly higher than those of neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency throughout the first 3 days of life (p=0.009 to 0.049). Most neonates with HE caused by the common SPTB mutations who required phototherapy did not exhibit anaemia and were not diagnosed clinically at birth. Coinheritance of the SPTB mutations and G6PD deficiency likely aggravated anaemia and worsened the degree of jaundice. HE caused by the three common SPTB mutations is associated with the development of significant jaundice requiring treatment among Thai neonates. Given the region's high prevalence, screening for the SPTB mutations is likely beneficial for comprehensive monitoring of neonatal jaundice and for disease counselling.