This disease is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, and increased levels of erythrocyte protoporphyrin.
The disease is caused by mutations in the gene STEAP3 (also known as TSAP6) that encodes a ferrireductase involved in the acquisition of iron by developing erythroblasts. So far only one family with 3 affected siblings have been reported with this disease. The prevalence is unknown.
This disease is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, resembling non-syndromic sideroblastic anemia (due to defects in SLC25A38 gene), but contrary to SLC25A38-CSA disease, in this disease an increased levels of erythrocyte protoporphyrin were detected. In the only family reported up to date, one of the affected patients shows growth retardation, massive hepatosplenomegaly and cafe-au-lait blotches on his skin. All affected patients had hypogonadism, with azoospermia in the males, and atrophy of the gonads in the female patient. A complex dysfunction of the hypothalamopituitary-gonadal axis was seen in all 3 patients, suggesting a primary defect of the gonads in addition to secondary hypogonadism. Latent adrenal and thyroid failure was detected in one patient.
Treatment is supportive and involves haematological monitoring with regular blood transfusions. The inclusion of EPO treatment may decrease the number of required blood transfusions. Iron overload should be monitored and treated with chelation therapy. Patients do not respond to treatment with vitamin B6 (pyridoxine).
Severe congenital hypochromic anemia with ringed sideroblasts due to mutations in STEAP3 gene is most likely to be inherited in an autosomal recessive manner. Only one family has been reported and the affected patients have one heterozygous nonsense mutation together with one low expression allele. An individual can be heterozygous for the disorder (healthy carrier) when only one of the STEAP3 allele is mutated, or homozygous or compound heterozygous (affected individual) when two STEAP3 alleles are mutated. A couple who carries each one a mutated STEAP3 allele have a 25 percent risk of having a child affected by the disorder at each pregnancy. The risk of having a child who is a healthy carrier of the disorder is 50 percent at each pregnancy, and the risk that a child will not have the disorder and will not be a carrier is 25 percent. Ask for genetic counselling to get a complete explanation.