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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.

Dejerine-Sottas disease (DSD) is a particular phenotype of the Charcot-Marie-Tooth (CMT) disease spectrum that is genetically heterogeneous. It represents a severe form of hypertrophic axonal and demyelinating neuropathy. Although it is predominantly inherited as an autosomal recessive condition, autosomal dominant inheritance has also been described. To date, the autosomal recessive forms of DSD are classified into several CMT type 4 (CMT4) subclasses based on allelic heterogeneity. We present a 7-year-old boy with a severe form of CMT disease consistent with the autosomal recessive phenotype of DSD. He was found to be a compound heterozygote for mutations in the PMP22 gene resulting in homozygous deletion of exons 2 and 3. The maternally inherited allele was the typical 1.5 Mb deletion involving PMP22 seen with hereditary neuropathy with liability to pressure palsy (HNPP). The paternally inherited allele was a deletion of exons 2 and 3. Both parents presented with a typical clinical picture of HNPP. To our knowledge, this is the first patient reported with large deletions involving both PMP22 alleles. Our patient has also developed severe gastroesophageal reflux disease (GERD), a clinical feature not previously reported with CMT or DSD. The correlation of the phenotype and the molecular defects observed in this patient may set a new subcategory in the classification of DSD.