Department of Paediatrics, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
Department of Endocrinology and Diabetes, Birmingham Women's and Children's NHS Foundation Trust Birmingham, Birmingham, UK.
Eur J Endocrinol. 2021 May;184(5):K15-K20. doi: 10.1530/EJE-20-0152.
Autosomal recessive forms of pseudohypoaldosteronism are caused by genetic defects in the epithelial sodium channel. Little is known about the long-term outcome and medication needs during childhood and adolescence.
This study reports a single-centre experience of children affected with this ultra-rare condition over a 37-year period.
We report the clinical presentation, growth, neuro-development, associated conditions, mortality and medication dosing and administration for 12 affected children from eight families.
All children were presented within the first 2 weeks of life with life-threatening, severe hyperkalaemia and hyponatraemia. All parents were consanguineous and of South Asian, Middle Eastern or African ethnic origin. Eight children had homozygous mutations in the SCNN1A and SCNN1G genes, encoding the epithelial sodium channel subunits alpha and gamma, respectively, including one novel mutation. Three children died (25%) and two (16%) had severe neurological impairment post-cardiac arrest secondary to hyperkalaemia. One affected female had a successful pregnancy at the age of 28 years.
Despite high mortality and morbidity in this condition, survival with normal physical and neurological outcome is possible, justifying intensive management to prevent electrolyte imbalance.
常染色体隐性遗传型假性醛固酮减少症是由上皮钠通道的基因缺陷引起的。对于儿童和青少年时期的长期预后和药物需求知之甚少。
本研究报告了一个单中心在 37 年期间对患有这种超罕见疾病的儿童的经验。
我们报告了 8 个家庭的 12 名受影响儿童的临床表现、生长、神经发育、相关疾病、死亡率以及药物剂量和管理。
所有儿童均在出生后 2 周内出现危及生命的严重高钾血症和低钠血症。所有父母均为近亲，来自南亚、中东或非洲裔。8 名儿童在 SCNN1A 和 SCNN1G 基因中均存在纯合突变，分别编码上皮钠通道亚基 alpha 和 gamma，包括一个新突变。3 名儿童死亡（25%），2 名（16%）因高钾血症继发心搏骤停后有严重神经功能障碍。一名受影响的女性在 28 岁时成功怀孕。
尽管这种疾病的死亡率和发病率很高，但通过积极的治疗，患儿可能存活下来并具有正常的身体和神经发育，因此有必要进行强化管理以预防电解质失衡。
