Resolution of refractory hypotension and anuria in a premature newborn with loss-of-function of ACE

• Published in: American journal of medical genetics. Part A 2015-07, Vol.167A (7), p.1654-1658
• Main Authors: Richer, Julie, Daoud, Hussein, Geier, Pavel, Jarinova, Olga, Carson, Nancy, Feberova, Jana, Nadya, Ben Fadel, Unrau, Jennifer, Bareke, Eric, Khatchadourian, Karine, Bulman, Dennis E, Majewski, Jacek, Boycott, Kym M, Dyment, David A
• Format: Article
• Language: English
• Subjects: ACE; Adult; Anuria - drug therapy; Anuria - genetics; Anuria - pathology; Base Sequence; Female; Fludrocortisone - therapeutic use; Frameshift Mutation - genetics; Gene Deletion; High-Throughput Nucleotide Sequencing; Humans; Hypotension - drug therapy; Hypotension - genetics; Hypotension - pathology; Infant, Newborn; Infant, Premature - physiology; Kidney Tubules, Proximal - abnormalities; Kidney Tubules, Proximal - pathology; Molecular Sequence Data; Neonatal Intensive Care Unit; next generation sequencing; oligohydramnios; Peptidyl-Dipeptidase A - genetics; Potter sequence; Pregnancy; renal tubular dysgenesis; Treatment Outcome; Urogenital Abnormalities - genetics; Urogenital Abnormalities - pathology; Vasopressins - therapeutic use
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37067

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1‐converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition. © 2015 Wiley Periodicals, Inc.