Department of Pediatric Acute Disease, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Department of Pediatrics, Fukuyama City Hospital, Fukuyama, Japan.
BMC Pediatr. 2022 Oct 29;22(1):622. doi: 10.1186/s12887-022-03706-3.
Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation.
A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation.
We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.
新生儿血色素沉着症在新生儿期引起急性肝衰竭，主要是由于妊娠同种免疫性肝病（GALD）。地中海贫血由于珠蛋白基因突变引起溶血性贫血和无效造血。尽管新生儿血色素沉着症和地中海贫血有完全不同的病因，但这些疾病的共存可能会协同加重铁过载。我们报告一例伴有 εγδβ-地中海贫血的新生儿发生新生儿血色素沉着症，铁螯合剂治疗无效且病情迅速恶化，需要进行活体肝移植。
一名 1 天龄的日本男婴因溶血性贫血和靶形红细胞接受基因检测诊断为 εγδβ-地中海贫血，需要频繁输血。出生后 2 个月，出现黄疸、灰白色粪便和血清铁蛋白水平升高，肝活检显示肝细胞和枯否细胞铁沉积。磁共振成像扫描显示肝脏、脾脏、胰腺和骨髓有铁沉积的表现。输入的红细胞总量未达到输血后铁过载的标准。开始给予铁螯合剂，但铁过载迅速进展为肝功能衰竭，黄疸和肝损伤无改善。他接受了来自母亲的活体肝移植，此后铁过载消失，未再发生铁过载。肝组织中 C5b-9 的免疫组化染色为阳性。活体肝移植前血清铁调素水平较低，生长分化因子 15 水平较高。
我们报告一例由 GALD 引起的 εγδβ-地中海贫血婴儿发生 NH，除红细胞输注外，无效造血的共存可能加重了铁过载。在此例中，血清铁调素水平较低可能是由于新生儿血色素沉着症导致胎儿肝损伤引起的铁调素生成减少，以及地中海贫血中观察到的无效造血引起的铁调素抑制性造血介质增加所致。
