背景:遗传性血色素沉着病是一种常染色体隐性遗传疾病,其中皮肤色素沉着和器官损伤的临床表型仅发生在纯合子中。简单的杂合子,也就是说,只是C282Y,通常不会出现铁过载。在这里,我们提出了一个案例,其中一个简单的杂合子与酒精中毒结合产生了高铁蛋白和高转铁蛋白饱和度,表明铁过载。虽然酗酒可以解释她的演讲,我们假设铁和酒精的炎症性混合物可能导致我们的患者在很小的时候就死于急性肝衰竭.
方法:一名29岁的白种人妇女到医院就诊,她的眼睛和皮肤因厌食症而逐渐变黄,恶心,呕吐,弥漫性腹部不适,增加腹围,深色尿液和苍白的粪便约2周。家族史对遗传性血色病具有重要意义。她的父亲是一个简单的杂合子,她的祖母是C282Y的纯合子。体格检查显示巩膜黄疸,腹部扩张伴肝肿大和轻度全身压痛。实验室检查结果显示白细胞计数升高,铁蛋白539ng/dL,转铁蛋白饱和度58.23%,肝酶升高,提高的国际标准化比率(INR),低白蛋白,酒精性肝病/非酒精性脂肪性肝病(ALD/NAFLD)指数(ANI)为2.6,提示酒精性肝病的概率为93.2%,磷脂酰乙醇水平为537ng/ml。基因检测显示,该患者是人类稳态铁调节蛋白(HFE)C282Y突变和正常等位基因的杂合子。腹部计算机断层扫描(CT)显示肝肿大,门静脉高压症和广泛性anasarca。磁共振胰胆管造影(MRCP)显示胆管病理阴性。其他肝病原因的检查结果为阴性。诊断为急性酒精性肝炎,在Maddrey的判别函数>32的情况下,开始使用泼尼松龙。尽管服用了类固醇,她的胆红素和INR继续增加,病人不幸死亡。
结论:我们的案例强调了在年轻肝功能衰竭患者的鉴别诊断中考虑血色素沉着病的重要性。包括暗示酒精中毒为可能病因的病例。需要进行更大规模的研究来研究非铁因素,如酒精和病毒性肝炎在遗传性血色素沉着症的简单杂合子肝病进展中的作用。鉴于这种突变在北欧血统人群中的患病率很高。
BACKGROUND: Hereditary hemochromatosis is an autosomal recessive disorder where the clinical phenotype of skin pigmentation and organ damage occurs only in homozygotes. Simple heterozygotes, that is, just C282Y, typically do not develop iron overload. Here we present a
case where a simple heterozygote in combination with alcoholism developed high ferritin and high transferrin saturation levels indicative of iron overload. Though alcoholism alone could explain her presentation, we hypothesize that an inflammatory cocktail of iron and alcohol probably caused our patient to succumb to acute liver failure at a very young age.
METHODS: A 29-year-old Caucasian woman presented to the hospital with progressively worsening yellowish discoloration of her eyes and skin associated with anorexia, nausea, vomiting, diffuse abdominal discomfort, increasing abdominal girth, dark urine and pale stools for about 2 weeks. Family history was significant for hereditary hemochromatosis. Her father was a simple heterozygote and her grandmother was homozygous for C282Y. Physical examination showed scleral icterus, distended abdomen with hepatomegaly and mild generalized tenderness. Lab test results showed an elevated white blood cell count, ferritin 539 ng/dL, transferrin saturation 58.23%, elevated liver enzymes, elevated international normalized ratio (INR), low albumin, Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease (ALD/NAFLD) Index (ANI) of 2.6, suggesting a 93.2% probability of alcoholic liver disease, and phosphatidyl ethanol level of 537ng/ml. Genetic testing showed that the patient was heterozygous for human homeostatic iron regulator protein (HFE) C282Y mutation and the normal allele. Computed tomography (CT) of the abdomen revealed hepatomegaly, portal hypertension and generalized anasarca. Magnetic resonance cholangiopancreatography (MRCP) showed negative results for bile duct pathology. Workup for other causes of liver disease was negative. A diagnosis of acute alcoholic hepatitis was made, with Maddrey\'s discriminant function of > 32, so prednisolone was started. Her bilirubin and INR continued to increase despite steroids, and the patient unfortunately died.
CONCLUSIONS: Our
case highlights the importance of considering hemochromatosis in the differential diagnosis of young patients presenting with liver failure, including cases suggestive of alcoholism as the likely etiology. Larger studies are needed to investigate the role of non-iron factors like alcohol and viral hepatitis in the progression of liver disease in simple heterozygotes with hereditary hemochromatosis, given the high prevalence of this mutation in persons of Northern European descent.