Objective: To analyze the clinical, genetic mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis (HH) in China. Methods: Peripheral blood samples and clinical data of patients with primary iron overload were collected through the China Registry of Genetic/Metabolic Liver Disease from June 2015 to November 2023. HH-related genes were detected by Sanger sequencing. Clinical characteristics and gene mutation characteristics of HH patients carrying HJV gene mutations were analyzed. Results: Among the 37 cases with primary iron overload, ten cases (27.0%, 10/37) had detectable HJV gene mutations, which included four homozygous mutations, five compound heterozygous mutations, and one monoheterozygous mutation. p.Q6H and p.C321X (80.0%, 8/10) were the most common mutated sites. The average age of onset was 30.7±14.7 years. The age of diagnosis was 35.7±16.2 years, with male-to-female ratio of 7:3. Ferritin and transferrin saturation were (5 267±905) ng/ml, and 94.3%±1.2%, respectively. Magnetic resonance imaging showed iron overload in the liver, pancreas, and myocardium. Liver biopsy showed diffuse iron deposition within hepatocytes. All ten cases had elevated transaminases; one case (1/10, 10.0%) had liver cirrhosis; four cases (4/10, 40.0%) had heart failure and arrhythmia; five cases (5/10, 50.0%) had diabetes; six cases (6/10, 60.0%) had hypogonadism; six cases (6/10, 60.0%) had skin pigmentation; and six cases (6/10, 60.0%) had fatigue symptoms. All six cases underwent bloodletting therapy, and ferritin levels dropped to about 100 ng/ml. Two cases of oral administration of the iron chelator deferasirox did not meet the ferritin level standard, and one case died from acute heart failure following a confirmed diagnosis during hospitalization. Conclusion: The HJV gene may be one of the main pathogenic genes of HH in China. The p.Q6H and p.C321X mutations were one of the hotspot mutations. The onset age of HJV gene-related HH was between 20 and 30 years old, and their condition was severe. Therefore, early bloodletting treatment can have a favorable outcome.
目的： 分析我国2A型遗传性血色病（HH）的临床、基因突变特征及其治疗预后。 方法： 自2015年6月至2023年11月通过中国遗传代谢性肝病注册研究网收集原发性铁过载患者的外周血样本、临床资料。采用Sanger测序法检测HH相关基因。对携带HJV基因突变的HH患者进行临床特征及基因突变特征分析。 结果： 在37例原发性铁过载患者中，10例（27.0%，10/37）检出HJV基因突变，其中4例为纯合突变，5例为复合杂合突变，1例单杂合突变，最常见的突变位点为p.Q6H和p.C321X（80.0%，8/10）。发病年龄（30.7±14.7）岁，诊断年龄（35.7±16.2）岁，男女之比为7∶3。铁蛋白（5 267±905）ng/ml，转铁蛋白饱和度94.3%±1.2%。核磁共振成像显示肝脏、胰腺、心肌均有铁过载；肝活检提示肝细胞内弥漫铁沉积。10例均有转氨酶增高，1例（1/10，10.0%）肝硬化，4例（4/10，40.0%）心功能不全、心律失常，5例（5/10，50.0%）糖尿病；6例（6/10，60.0%）性腺功能下降；6例（6/10，60.0%）皮肤色素沉着；6例（6/10，60.0%）有乏力症状。6例进行放血疗法，铁蛋白均已降至100 ng/ml左右；2例口服铁螯合剂地拉罗司，铁蛋白未达标；1例住院明确诊断后因急性心力衰竭死亡。 结论： HJV基因可能是我国HH的主要致病基因之一，p.Q6H和p.C321X突变是热点突变位点。HJV基因相关HH发病年龄介于20～30岁，病情重，如及早放血治疗，预后好。.