Aşırı demir yüklenmesi ve hemokromatozis

Öz

Giriş ve Amaç: Uzun süreli (on yıl) takip ettiğimiz aşırı demir yüklenmesi ve hemokromatozis olgularımız ışığında ortaya çıkan bulguları, tanı ve tedavideki zorlukları ve eksik yanlarımızı değerlendirmeyi amaçladık. Gereç ve Yöntem: 2012-2022 yılları arasında takip ettiğimiz, aşırı demir birikimi olan hastalar bilgisayar kayıtlarından retrospektif olarak değerlendirildi. Transferrin satürasyonu %45’ten yüksek ve serum ferritin düzeyleri erkeklerde 300 ng/dl, kadınlarda 200 ng/dl’den yüksek olan toplam 28 hasta saptandı. Hastalarda hemokromatozis için genetik testler yapıldı. Genetik testlerin pozitif veya negatif oluşuna göre hastalar analiz edildi. Bulgular: Toplam 28 hastadan 17’si H63D heterozigot, bir hasta H63D homozigot olarak bulundu. C282Y ve non-HFE hemokromatozise ait gen mutasyonu saptanmadı. On hastada herhangi bir mutasyon saptanmadı. Yirmi sekiz hastanın tümünde transferrin satürasyonu %45’ten büyük ve ferritin düzeyi 300 ng/dl’den yüksekti. H63D heterozigot bulunanların 10’unda (%58.8), mutasyon saptanmayanların 5’inde (%50) hepatosteatoz saptandı. Heterozigot pozitif olan grupta mutasyon saptanmayanlara göre demir birikimi biraz daha yüksekti (ortalama ferritin düzeyi 1478 ng/dl’ye 827ng/dl). Hastaların hepsinde hepatit B yüzey antijeni negatifti. Bir hastada anti-hepatit C virüsü pozitifti. Magnetik rezonans çekilen 16 hastada demir yüklenmesi düşündüren sinyal kaybı bulgusu bildirilmedi. Still hastalığına ilişkin ateş, artralji gibi bir bulgu saptanmadı. Sonuçlar: Aşırı demir yüklenmesi sık karşılaşılan bir durum olmamakla birlikte saptandığında ayırıcı tanısı zordur. Herediter hemokromatozis ve non-HFE hemokromatozis bunların çok az bir kısmını oluşturur. Bulgularımız aşırı demir birikmesinin en sık sebeplerinden birinin non-alkolik yağlı karaciğer hastalığına bağlı olduğunu göstermektedir.

Anahtar Kelimeler

• Aşırı demir birikimi
• hemokromatozis
• genetik test

Iron overload and hemochromatosis

Öz

Background and Aims: We aimed to evaluate the findings, difficulties in diagnosis and treatment, and our shortcomings in the light of iron overload and hemochromatosis cases that we followed for a long time (ten years). Materials and Methods: Patients with excessive iron overload that we followed between 2012 and 2022 were evaluated retrospectively from computer records. A total of 28 patients with transferrin saturation higher than 45% and serum ferritin levels higher than 300 ng/dl in men and 200 ng/dl in women were detected. Genetic testing for hemochromatosis was performed on the patients. Patients were analyzed according to whether the genetic tests were positive or negative. Results: Of the 17 of 28 patients were H63D heterozygous and 1 was H63D homozygous. No gene mutations of C282Y and non-HFE hemochromatosis were detected. No mutation was detected in 10 patients. Transferrin saturation was greater than 45 percent and ferritin level was higher than 300 ng/dl in all 28 patients. No patient received blood transfusion. Hepatosteatosis was detected in 10 (58.8%) of those with H63D heterozygous and 5 (50%) of those without mutation. Iron accumulation was slightly higher in the heterozygous positive group than in those without mutations (mean ferritin level 1478 ng/dl vs. 827 ng/dl). All patients were negative for hepatitis B surface antigen. One patient was anti-hepatitis C virus positive. Signal loss suggestive of iron overload was not reported in 16 patients who underwent magnetic resonance imaging. There was no finding related to Still's disease such as fever or arthralgia. Conclusions: Although iron overload is not a common condition, its differential diagnosis is difficult when detected. Hereditary hemochromatosis and non-HFE hemochromatosis constitute only a small part of them. Our findings show that one of the most common causes of excessive iron accumulation is due to non-alcoholic fatty liver disease.

Anahtar Kelimeler

• Iron overload
• hemochromatosis
• genetic testing

Kaynakça

1. 1-Bacon BR, Fleming RE. Hemochromatosis. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th ed, Feldman M, Friedman L, Brandt L (Eds), Elsevier, 2020. p1071-80.
2. 2-Bacon BR, Kwiatkowski JL. Approach to the patient with suspected iron overload. Uptodate. Literature review current through: May 2022. | This topic last updated: Jun 09, 2022.
3. 3-Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol 2019;114:1202-18.
4. 4-McLaren GD, Gordeuk VR. Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Hematology Am Soc Hematol Educ Program 2009;195-206.
5. 5-Uguen K, Scotet V, Ka C, et al. Diagnostic value of targeted next-generation sequencing in suspected hemochromatosis patients with a single copy of the HFE p.Cys282Tyr causative allele. Am J Hematol 2017;92:E664-E666.
6. 6-Yönal O, Hatirnaz O, Akyüz F, et al. HFE gene mutation, chronic liver disease, and iron overload In Turkey. Dig Dis Sci 2007;52:3298-302.
7. 7- Şimşek H, Shorbagi A, Tatar G. What is the future of research for hereditary hemochromatosis in Turkey. Turk J Gastroenterol 2013;24:1-4.
8. 8- Datz C, Müller E, Aigner E. Iron overload and non-alcoholic fatty liver disease. Minerva Endocrinol 2017;42:173-83.

9. 9- Rametta R, Fracanzani AL, Fargion S, Dongiovanni P. Dysmetabolic hyperferritinemia and dysmetabolic iron overload syndrome (DIOS): Two related conditions or different entities? Curr Pharm Des 2020;26:1025-35.
10. 10- Rametta R, Dongiovanni P, Pelusi S, et al. Hepcidin resistance in dysmetabolic iron overload. Liver Int 2016;36:1540-8.
11. 11-Ye Q, Qian BX, Yin WL, et al. Association between the HFE C282Y, H63D polymorphisms and the risks of non-alcoholic fatty liver disease, liver cirrhosis and hepatocellular carcinoma: An updated systematic review and meta-analysis of 5,758 cases and 14,741 controls. PLoS One 2016;11:e0163423. Epub 2016 Sep 22.
12. 12 - Pietrangelo A. Iron and the liver. Liver Int 2016; 36(Suppl 1):116-23.
13. 13- Camaschella C. Iron and hepcidin: a story of recycling and balance. Hematology Am Soc Hematol Educ Program 2013;2013:1-8.
14. 14- Pietrangelo A. Genetics, genetic testing, and management of hemochromatosis: 15 years since hepcidin. Gastroenterology 2015;149:1240-51.
15. 15- Kelley M, Joshi N, Xie Y, Borgaonkar M. Iron overload is rare in patients homozygous for the H63D mutation. Can J Gastroenterol Hepatol 2014;28:198-202.