A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene.

STEAP3/TSAP6 encodes a ferrireductase that is involved in the acquisition of iron by developing erythroblasts and steap3/tsap6 null-mice display severe microcytic anemia. We report a family in which 3 siblings born to healthy parents display transfusion-dependent hypochromic anemia. A nonsense STEAP3/TSAP6 was identified in the siblings at the heterozygous state. This mutation was inherited from their father while no mutation was found in their mother. A large variability of expression was found between normal alleles in a control population, confirming a previous report that STEAP3/TSAPS6 is an expressed quantitative trait locus (e-QTL). Determination of the relative allele expression showed that the "normal" allele was expressed at a significantly higher level in the father than in the affected siblings relative to the shared mutated allele. The blood level of STEAP3/TSAP6 mRNA was severely reduced in the siblings, while both parents were in the lower range of normal controls. The STEAP3/TSAP6 protein was also reduced in lymphocytic cell lines from the patients. Collectively, our data support the hypothesis that STEAP3/TSAP6 deficiency leads to severe anemia in the affected siblings and results from the combination of a mutated allele inherited from their father and a weakly expressed allele inherited from their mother.

Polycythemia and Hb Coimbra [beta 99 (G1) Asp -> Glu] in Brazil

We report the clinical and laboratory findings concerning three unrelated Brazilian patients investigated for polycythemia, whose definitive diagnosis could only be established after the presence of Hb Coimbra (b99 Asp ® Glu) was demonstrated. This illustrates the importance of properly investigating hereditary hemoglobinopathies in cases of erythrocytosis because in some populations variants with high oxygen affinity may be more frequent than expected but go undetected when conventional electrophoresis is used as the sole detection procedure.

Iron deficiency anaemia in newborn sla mice: a genetic defect of placental iron transport.

Newborn mice with X-linked anaemia (gene symbol sla) have lower haemoglobin levels at birth than normal and carrier mice but there is considerable overlap. Serial observations showed that the haemoglobin values of segregating male mice separate into a bimodal distribution of 42 d of age, and 50 d values were used to assign genotypes retrospectively. The anaemia in newborn sla mice is attributable to iron deficiency, since their total body iron is lower than in normal newborn mice, while their birth weights are almost identical. Haemoglobin levels at birth in normal, anaemic and carrier mice are also influenced by the mother's genotype and phenotype, and the haemoglobin value was progressively lower according to the sla gene dose of the mother. Materno-fetal iron transfer was examined by labelling pregnant carrier females with radioiron in various ways. When given as single or intermittent doses by injection no clearcut differences emerged in apparent iron transfer to anaemic as compared to non-anaemic fetuses. However, when radioiron was administered continuously in food a significant reduction in iron transfer to anaemic fetuses was demonstrated. The sla gene is already known to have a major effect in reducing iron transport in the small intestine. The present studies provide evidence of an analogous defect in placental iron transport.

Hematology of the neonatal calf. III. Frequency of congenital iron deficiency anemia.

The hematocrits of 258 Holstein-Friesian and Jersey calves were determined during the first 3 days following birth. Hematocrit values of 25% or less were observed in 15.8% of the calves and hematocrits of 20% or less were observed in 6.9% of calves from apparently normal dams. The serum iron concentration of neonatal calves with hematocrits of 25% or less was significantly lower than the value recorded in calves with hematocrits above 25% and there was a direct correlation between PCV and serum iron concentration. The data presented suggested that prenatal development of iron deficiency is an important cause of anemia in neonatal dairy calves. Factors which may be important in pathogenesis are discussed.