Kelly A L, Rhodes D A, Roland J M, Schofield P, Cox T M
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
QJM. 1998 Sep;91(9):607-18. doi: 10.1093/qjmed/91.9.607.
Juvenile haemochromatosis is a rare inborn error of iron metabolism with clinical manifestations before 30 years of age. Unlike adult haemochromatosis which principally affects men, juvenile haemochromatosis affects the sexes equally; it causes early endocrine failure, dilated cardiomyopathy and joint disease. We report four patients (two of each sex) from three pedigrees affected by juvenile haemochromatosis with a mean onset at 22 years (range 14-30). All had endocrine deficiency with postpubertal gonadal failure secondary to pituitary disease; two suffered near-fatal cardiomyopathy with heart failure. Mean time to diagnosis from the first clinical signs of disease was 9.8 years (range 0.5-20) but general health and parameters of iron storage responded favourably to iron-depletion therapy. A 24-year-old man listed for heart transplantation because of cardiomyopathy [left ventricular (LV) ejection fraction 16%] responded to intravenous iron chelation with desferrioxamine combined with phlebotomy (ejection fraction 31%). A 27-year-old woman with subacute biventricular heart failure refractory to medication required orthotopic cardiac transplantation before the diagnosis was established (LV ejection fraction 25%). Genetic studies showed that these two patients with cardiomyopathy from unrelated families were heterozygous for the HFE 845G-->A (C282Y) mutation and wild-type at the H63D locus: complete sequencing of the intron-exon boundaries and entire coding sequence of the HFE gene failed to identify additional lesions. Two siblings in a pedigree without cardiomyopathy were wild-type at the HFE C282Y locus; although the brother harboured a single copy of the 187C-->G (H63D) allele, segregation analysis showed that in neither sibling was the iron-storage disease linked to MHC Class I markers on chromosome 6p. Juvenile haemochromatosis is thus a genetically heterogenous disorder distinct from the common adult variant.
青少年血色素沉着症是一种罕见的先天性铁代谢紊乱疾病，在30岁之前出现临床表现。与主要影响男性的成人血色素沉着症不同，青少年血色素沉着症对男女影响相同；它会导致早期内分泌功能衰竭、扩张型心肌病和关节疾病。我们报告了来自三个家系的4例青少年血色素沉着症患者（男女各2例），平均发病年龄为22岁（范围14 - 30岁）。所有患者都有内分泌缺陷，青春期后性腺功能衰竭继发于垂体疾病；2例患者患有近乎致命的心肌病并伴有心力衰竭。从疾病的首个临床症状到确诊的平均时间为9.8年（范围0.5 - 20年），但总体健康状况和铁储存参数对铁耗竭疗法反应良好。一名因心肌病（左心室射血分数16%）而被列入心脏移植名单的24岁男性，对静脉注射去铁胺联合放血的铁螯合疗法有反应（射血分数31%）。一名患有亚急性双心室心力衰竭且药物治疗无效的27岁女性，在确诊前需要进行原位心脏移植（左心室射血分数25%）。基因研究表明，这两名来自无关家族的心肌病患者在HFE 845G→A（C282Y）突变位点为杂合子，在H63D位点为野生型：对HFE基因的内含子 - 外显子边界和整个编码序列进行完整测序未能发现其他病变。一个家系中没有心肌病的两名兄弟姐妹在HFE C282Y位点为野生型；尽管哥哥携带187C→G（H63D）等位基因的单拷贝，但分离分析表明，这两名兄弟姐妹中均未发现铁储存疾病与6号染色体p臂上的MHC I类标记相关。因此，青少年血色素沉着症是一种与常见成人型不同的基因异质性疾病。
