Mutation Analysis in Iron Deficiency Anemia of Undeterminable Etiology

Iron deficiency is the main cause of anemia worldwide. Iron deficiency anemia (IDA) occurs under such conditions as insufficient intake (when requirements increase or under normal conditions) or when losses cannot be met by intake. IDA may also rarely be seen in rare situations such as when absorbance is insufficient or in the presence of specific gene defects. Iron deficiency generally occurs in the event of increased losses by physiological routes, such as menstruation, and is therefore more common in women. The etiology in an adult male or postmenopausal woman is frequently gastrointestinal bleeding. A tumoral formation in the gastrointestinal system is usually present in the etiology of such bleeding. In etiological terms, if a cause cannot be identified with routine screening, then rare causes must be considered, including hematuria, hemosiderosis, celiac disease, pica, and genetic disorder affecting iron use. In this study we screened 455 patients meeting the criteria for iron deficiency. IDA that failed to respond to iron therapy and that recurred after treatment was identified in 10 of these patients. Sequencing analysis using the Sanger method was performed on the 13th exon of gene TMPRSS6, which encodes the protein matriptase-2, in 10 patients in whom no etiology could be determined despite all investigations. Although mutation in the TMPRSS6 gene was not observed in these cases, single-gene polymorphism was observed in some patients. Single gene polymorphisms in TMPRSS6 are common in society and are known to play a role in the development of IDA. Single D521D gene mutation was observed in five of the 10 individuals we selected

MUTATION ANALYSIS IN IRON DEFICIENCY ANEMIA OF UNDETERMINABLE ETIOLOGY

Demir eksikliği tüm dünyada karşılaşılan en sık anemi nedenidir. Demir eksikliği anemisi (DEA), alım yetersizliği (ihtiyacın arttığı durumlarda ya da normal şartlarda) ya da alımın karşılayamadığı kayıp durumlarında gelişebilmektedir. Emilimin yetersiz olduğu ya da belirli gen defektleri varlığındaki gibi nadir durumlar sonucunda da DEA görülebilmektedir. Genelde menstruasyon gibi fizyolojik yolla olan kayıpların arttığı durumlarda, dolayısıyla daha çok kadınlarda demir eksikliğine rastlanır. Erişkin bir erkek veya postmenapozal dönemdeki kadında ise etiyoloji sıklıkla gastrointestinal kanamadır. Kanamaların etyolojisinde ise çoğunlukla GİS’teki bir tümoral oluşum bulunmaktadır. Eğer etyoloji açısından rutin taramalarla neden bulunamazsa nadir sebepler akla gelmelidir; hematüri, hemosiderozis, çölyak hastalığı, pica, demir kullanımını etkileyen genetik bozukluk gibi. Biz çalışmamızda demir eksikliği kriterlerini karşılayan 455 hasta taradık. Bu hastalardan 10’ unda, demir tedavisine cevap alınmamış ve tedavi sonrasında DEA’sı tekrarlamakta idi. Bütün araştırmalara rağmen etiyolojisi belirlenemeyen bu 10 hastada, matriptaz-2 proteinini kodlayan TMPRSS6 geninin 13. eksonuna Sanger metodu ile dizileme analizi yapıldı. Bu hastalarda TMPRSS6 geninde mutasyon izlenmese de bazı hastalarda tekli gen polimorfizmi görüldü. TMPRSS6’daki tekli gen polimorfizmleri toplumda sık görülmekle beraber DEA gelişiminde rol oynadığı bilinmektedir. Bizim seçtiğimiz 10 kişinin 5’inde de D521D tekli gen mutasyonu izlendi.Iron deficiency is the main cause of anemia worldwide. Iron deficiency anemia (IDA) occurs under such conditions as insufficient intake (when requirements increase or under normal conditions) or when losses cannot be met by intake. IDA may also rarely be seen in rare situations such as when absorbance is insufficient or in the presence of specific gene defects. Iron deficiency generally occurs in the event of increased losses by physiological routes, such as menstruation, and is therefore more common in women. The etiology in an adult male or postmenopausal woman is frequently gastrointestinal bleeding. A tumoral formation in the gastrointestinal system is usually present in the etiology of such bleeding. In etiological terms, if a cause cannot be identified with routine screening, then rare causes must be considered, including hematuria, hemosiderosis, celiac disease, pica, and genetic disorder affecting iron use. In this study we screened 455 patients meeting the criteria for iron deficiency. IDA that failed to respond to iron therapy and that recurred after treatment was identified in 10 of these patients. Sequencing analysis using the Sanger method was performed on the 13th exon of gene TMPRSS6, which encodes the protein matriptase-2, in 10 patients in whom no etiology could be determined despite all investigations. Although mutation in the TMPRSS6 gene was not observed in these cases, singlegene polymorphism was observed in some patients. Single gene polymorphisms in TMPRSS6 are common in society and are known to play a role in the development of IDA. Single D521D gene mutation was observed in five of the 10 individuals we selected