title: Resolution of refractory hypotension and anuria in a premature newborn with loss-of-function of ACE.
abstract: 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.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Richer
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.|Division of Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Geier
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Jarinova
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Carson
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Jana
authors.initials: J
authors.lastname: Feberova
authors.forename: Nadya
authors.initials: N
authors.lastname: Ben Fadel
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Nadya Ben
authors.initials: NB
authors.lastname: Fadfel
authors.affiliation: Division of Neonatology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Unrau
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montréal, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Bareke
authors.affiliation: Division of Endocrinology, Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Khatchadourian
authors.affiliation: Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Bulman
authors.affiliation: McGill University and Genome Quebec Innovation Centre, Montréal, Québec, Canada.
authors.forename: Jacek
authors.initials: J
authors.lastname: Majewski
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Kym M
authors.initials: KM
authors.lastname: Boycott
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.|Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Dyment
mesh_terms: D000328:Adult; D001002:Anuria / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D005260:Female; D005438:Fludrocortisone / Q000627:therapeutic use; D016368:Frameshift Mutation / Q000235:genetics; D017353:Gene Deletion; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007022:Hypotension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000002:abnormalities / Q000473:pathology; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011247:Pregnancy; D016896:Treatment Outcome; D014564:Urogenital Abnormalities / Q000235:genetics / Q000473:pathology; D014667:Vasopressins / Q000627:therapeutic use*
chemical_list: D014667:Vasopressins; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D005438:Fludrocortisone
keywords: ACE; Neonatal Intensive Care Unit; Potter sequence; next generation sequencing; oligohydramnios; renal tubular dysgenesis