Aceruloplasminemia is a rare form of brain iron overload of autosomal recessive inheritance that results from mutations in the CP gene, encoding the iron oxidase ceruloplasmin. Homozygous aceruloplasminemia causes progressive neurodegenerative disease, anemia, and diabetes, and is usually diagnosed late in life upon investigation of anemia, high ferritin, or movement disorders, but its heterozygous state is less characterized and believed to be silent. Here we report two heterozygotes for new mutations causing aceruloplasminemia from whom peripheral blood samples were collected for complete blood counts, iron studies, and genotyping by automated sequencing. We then performed a systematic review of preview reports of heterozygotes with data on genotype and clinical findings. Heterozygosity for aceruloplasminemia invariably causes reduced ceruloplasmin levels, and similarly to previews reports in the literature, our cases did not present with anemia. Mild hyperferritinemia was found only in two reports. Nevertheless, 5 out of 11 variants have been associated with significant neurological symptoms despite the presence of one wild-type alelle. This review contributes to better genetic counseling of heterozygotes for CP gene variants and supports that measuring ceruloplasmin levels may be useful when investigating patients with movement disorders or rare cases of unexplained high ferritin.

中文翻译：

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杂合症与铜蓝蛋白血症的临床相关性。

铜绿蛋白血症是常染色体隐性遗传的脑铁超负荷的一种罕见形式，它是由CP基因的突变导致的，该基因编码铁氧化酶铜蓝蛋白。纯合子铜蓝蛋白血症会导致进行性神经退行性疾病，贫血和糖尿病，通常在调查贫血，高铁蛋白或运动障碍时被诊断为生命晚期，但其杂合状态的特征较少，被认为是沉默的。在这里，我们报告了两个新突变导致的铜蓝蛋白血症的杂合子，从中收集了外周血样本进行全血细胞计数，铁研究和通过自动测序进行基因分型。然后，我们对杂合子的预览报告进行了系统的综述，并提供了有关基因型和临床发现的数据。铜蓝蛋白血症的杂合性总是会导致铜蓝蛋白水平降低，并且与文献中的先行报道相似，我们的病例并未出现贫血。仅在两项报告中发现轻度高铁蛋白血症。尽管如此，尽管存在一种野生型alelle，但11种变体中有5种仍与明显的神经系统症状有关。这项审查有助于更好地为CP基因变异杂合子的遗传咨询，并支持在调查运动障碍患者或罕见原因不明的高铁蛋白患者时，测量铜蓝蛋白水平可能有用。尽管存在一种野生型alelle，但11种变体中有5种与明显的神经系统症状有关。这项审查有助于更好地为CP基因变异杂合子的遗传咨询，并支持在调查运动障碍患者或罕见原因不明的高铁蛋白患者时，测量铜蓝蛋白水平可能有用。尽管存在一种野生型alelle，但11种变体中有5种与明显的神经系统症状有关。这项审查有助于更好地为CP基因变异杂合子的遗传咨询，并支持在调查运动障碍患者或罕见原因不明的高铁蛋白患者时，测量铜蓝蛋白水平可能有用。