Comprehensive Genomic Analysis Identifies a Diverse Landscape of Sideroblastic and Nonsideroblastic Iron-Related Anemias with Novel and Pathogenic Variants in an Iron-Deficient Endemic Setting.

Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.

Women in Selected Communities of Punjab, India Have a High Prevalence of Iron, Zinc, Vitamin B12, and Folate Deficiencies: Implications for a Multiply-Fortified Salt Intervention.

Dietary intake and biomarkers of micronutrient status of 100 non-pregnant women of reproductive age (NPWRA) were assessed to determine optimal levels of iron, zinc, vitamin B12, and folic acid to include in multiply-fortified salt (MFS) that will be evaluated in an upcoming trial. Weighed food records were obtained from participants to measure intake of micronutrients and discretionary salt, and to assess adequacy using Indian Nutrient Reference Values (NRVs). Statistical modeling was used to determine optimal fortification levels to reduce inadequate micronutrient intake while limiting intake above the upper limit. Fasting blood samples were obtained to assess iron, zinc, vitamin B12, and folate status. In usual diets, inadequate intake of iron (46%), zinc (95%), vitamin B12 (83%), and folate (36%) was high. Mean intake of discretionary salt was 4.7 g/day. Prevalence estimates of anemia (37%), iron deficiency (67%), zinc deficiency (34%), vitamin B12 insufficiency (37%), and folate insufficiency (70%) were also high. Simulating the addition of optimized MFS to usual diets resulted in percentage point (pp) reductions in inadequate intake by 29 pp for iron, 76 pp for zinc, 81 pp for vitamin B12, and 36 pp for folate. MFS holds potential to reduce the burden of micronutrient deficiencies in this setting.

Effect of micronutrient supplementation around calving on the plasma cortisol levels of Murrah buffaloes and Sahiwal and Karan Fries cows.

Micronutrients when fed around peripartum may reduce the stress induced by cortisol. With this objective, 24 Sahiwal (SW) and 24 Karan Fries (KF) cows and 24 Murrah (Mu) buffaloes were taken and divided into four groups of six each. Vitamin E (VE), zinc (Zn) and copper were supplemented from 30 days pre- to 30 days postcalving in groups 1, 2 and 3. Animals without supplementation served as control. Blood sampling was done on days 30, 15, 7 and 3 precalving; at calving; and on days 3, 7, 15 and 30 postcalving. Plasma cortisol levels were measured by ELISA. Supplementation of VE and Zn significantly (P<0.05) reduced plasma cortisol levels at calving and at 30 days postcalving. KF cows exhibited best results with VE, whereas SW cows and Mu buffaloes responded best to Zn. Copper increased the peripartum cortisol levels. Reduction in cortisol levels may help in keeping the animal healthy and stronger to fight immuno-suppression generally observed around the period of peripartum.