Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Eur J Pediatr. 2012 Oct;171(10):1559-62. doi: 10.1007/s00431-012-1792-7. Epub 2012 Jul 17.
Aldosterone synthase (P450c11AS) deficiency is a rare autosomal recessive disorder, presenting with severe salt-losing in early infancy. It is caused by inactivating mutations of the CYP11B2 gene. Here, we describe three unrelated Asian patients who have clinical and hormonal features compatible with aldosterone synthase deficiency and identify their CYP11B2 mutations. Patient 1 was a Thai female infant. Patient 2 was an Indian boy, and patient 3 was a Thai male infant. All subjects presented at the age of 1-2 months with diarrhea, failure to thrive, and severe dehydration. Their plasma electrolytes showed hyponatremia, hyperkalemia, and acidosis. All patients had normal cortisol response and had elevated plasma renin activity with low aldosterone levels. The entire coding regions of the CYP11B2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a previously described mutation, p.T318M. Patient 2 was homozygous for a novel c.666delC mutation inherited from both parents resulting in p.223F>Sfsx295. No CYP11B2 mutation was detected in patient 3.
We report the first CYP11B2 defects in Southeast Asian families responsible for aldosterone synthase deficiency and identified a novel CYP11B2 mutation. However, the affected gene(s) responsible for primary hypoaldosteronism other than CYP11B2 remain to be determined.
醛固酮合酶（P450c11AS）缺乏症是一种罕见的常染色体隐性遗传病，在婴儿早期表现为严重的盐丢失。它是由 CYP11B2 基因的失活突变引起的。在这里，我们描述了三个无关的亚洲患者，他们具有与醛固酮合酶缺乏症相兼容的临床和激素特征，并确定了他们的 CYP11B2 突变。患者 1 是一名泰国女性婴儿。患者 2 是一名印度男孩，患者 3 是一名泰国男性婴儿。所有患者均在 1-2 个月龄时出现腹泻、生长不良和严重脱水。他们的血浆电解质显示低钠血症、高钾血症和酸中毒。所有患者的皮质醇反应正常，血浆肾素活性升高，醛固酮水平降低。通过聚合酶链反应扩增 CYP11B2 基因的整个编码区并进行测序。患者 1 是先前描述的突变 p.T318M 的纯合子。患者 2 是从父母双方遗传的 novel c.666delC 突变的纯合子，导致 p.223F>Sfsx295。患者 3 未检测到 CYP11B2 突变。
我们报告了首个导致醛固酮合酶缺乏症的 CYP11B2 缺陷在东南亚家族中的病例，并鉴定了一种 novel CYP11B2 突变。然而，除 CYP11B2 之外，导致原发性低醛固酮血症的受影响基因（s）仍有待确定。
