Department of Medical Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
University of Ottawa, Ottawa, Ontario, Canada.
Mol Genet Genomic Med. 2022 May;10(5):e1920. doi: 10.1002/mgg3.1920. Epub 2022 Mar 14.
Autosomal-recessive renal tubular dysgenesis (AR-RTD) is a rare genetic disorder caused by defects in the renin-angiotensin system that manifests as fetal anuria leading to oligohydramnios and Potter sequence. Although the most common outcome is neonatal death from renal failure, pulmonary hypoplasia, and/or refractory arterial hypotension; several cases have been reported that describe survival past the neonatal period.
Herein, we report the first family with biallelic ACE variants and more than one affected child surviving past the neonatal period, as well as provide a review of the previously reported 18 cases with better outcomes.
While both siblings with identical compound heterozygous ACE variants have received different treatments, neither required renal replacement therapy. We show that both vasopressin and fludrocortisone in the neonatal period may provide survival advantages, though outcomes may also be dependent on the type of gene variant, as well as other factors.
While AR-RTD is most often a lethal disease in the neonatal period, it is not universally so. A better understanding of the factors affecting survival will help to guide prognostication and medical decision-making.
常染色体隐性肾小管发育不良（AR-RTD）是一种罕见的遗传疾病，由肾素-血管紧张素系统缺陷引起，表现为胎儿无尿导致羊水过少和/或波特序列。尽管最常见的结局是新生儿因肾衰竭、肺发育不良和/或难治性动脉低血压而死亡；但已有几例报告描述了存活至新生儿期以后的情况。
本文报告了首例具有双等位基因 ACE 变异且有多个受影响儿童存活至新生儿期以后的家族，并对之前报道的 18 例预后较好的病例进行了回顾。
虽然具有相同复合杂合 ACE 变异的两个兄弟姐妹接受了不同的治疗，但均无需肾脏替代治疗。我们表明，新生儿期使用血管加压素和氟氢可的松可能具有生存优势，但结局也可能取决于基因变异的类型以及其他因素。
尽管 AR-RTD 在新生儿期通常是一种致命疾病，但并非普遍如此。更好地了解影响生存的因素将有助于指导预后和医疗决策。
