Aldosterone synthase deficiency is a rare cause of neonatal salt-wasting and failure to thrive. Routine newborn electrolyte screening after 5 days of life is vital for early detection and prevention of life-threatening crises. Genetic confirmation enables targeted fludrocortisone therapy, ensuring favorable growth and developmental outcomes.

Bartter syndrome (BS) is a rare group of inherited renal tubulopathies. Diagnosis of BS type II is challenging in the neonatal period as its clinical findings and biochemical features may mimic that of adrenal crisis and pseudo-hypoaldosteronism (PHA) initially. Treatment should be instituted immediately for acute adrenal insufficiency as it is a medical emergency, then modified according to available investigation results and treatment response. We describe a premature female neonate with an antenatal history of severe unexplained polyhydramnios, presented with features of adrenal crisis managed with hydrocortisone and fludrocortisone. Initial endocrine investigations excluded salt-wasting congenital adrenal hyperplasia (SW-CAH) and pointed to the diagnosis of PHA with hyperreninemic hyperaldosteronism. Hydrocortisone was gradually weaned off while fludrocortisone was continued for sodium retention effect. Hyperkalemia quickly transited into hypokalemia requiring high potassium requirement. Clinical and biochemical features of BS gradually evolved with polyuria, excessive weight loss, hypochloremic metabolic alkalosis and hypercalciuria at 1 week of age. Urgent trio whole exome sequencing (WES) subsequently confirmed the diagnosis of BS type II where compound heterozygous missense variants were identified in the KCNJ1 gene, one of which was a novel variant. Fludrocortisone was stopped and indomethacin was started with favorable outcomes. Though hypokalemia is the key feature of BS, transient hyperkalemia can occur in the early neonatal period in BS type II. Antenatal history should be enquired thoroughly to look for presence of severe unexplained polyhydramnios. The diagnosis of BS type II should be considered if other biochemical features are present. Genetic tests are important to provide a definite diagnosis and guide subsequent management and genetic counselling.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare monogenic kidney disorder characterized by progressive tubular atrophy and interstitial fibrosis. It is primarily associated with pathogenic variants in genes such as UMOD (uromodulin), REN (renin), MUC1 (mucin 1), and HNF1B (hepatocyte nuclear factor 1-beta). We report a unique Chinese case of ADTKD-UMOD in a patient carrying a UMOD gene mutation. The clinical presentation was complex: in addition to the classic features of UMOD mutations (hyperuricemia and gout), the patient exhibited endocrine and metabolic abnormalities typically linked to REN gene defects (ADTKD-REN), including anemia, hypotension, and hyporeninemic hypoaldosteronism. However, renal biopsy and genetic testing ultimately confirmed the diagnosis as ADTKD caused by a heterozygous missense mutation in UMOD gene.

A 3-year-old boy presented with polyuria and polydipsia for 18 months, along with growth failure. He was born prematurely, at 34 weeks of gestation, with a low birth weight. On examination, the child was severely underweight and hypertensive. Clinical history and evaluation could not identify any secondary causes of hypertension. There was no significant family history. An endocrine workup was planned, considering hypokalemia and metabolic alkalosis. This demonstrated hyporeninemic hypoaldosteronism and raised the possibility of apparent mineralocorticoid excess (AME) and Liddle syndrome. Clinical exome sequence analysis of HSD11B2 revealed a homozygous mutation in exon 5 (911A>G; p.His304Arg), which resulted in a missense mutation that confirmed the diagnosis of AME. A novel homozygous variant was found in the HSD11B2 gene in a subject with early onset hypertension associated with hypokalemic metabolic alkalosis, establishing the diagnosis of AME. Isolated aldosterone deficiency in children related either to impaired secretion by the adrenal gland or to aldosterone resistance in target tissues is rare. The incidence is estimated to be <1:1,000,000 for congenital isolated primary hypoaldosteronism and 1:66,000 to 1:166,000 for congenital aldosterone resistance (1). Children may present with salt wasting, hyponatremia, hypotension, hyperkalemia, metabolic acidosis, and failure to thrive. There is a wide phenotypic spectrum based on the severity and etiology of aldosterone deficiency or action. In this chapter, we briefly discuss the physiology of mineralocorticoids in newborns, categorize the causes of isolated hypoaldosteronism, and review the etiologies to guide clinical and laboratory evaluation and treatment. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Aldosterone synthase deficiency (ASD) is a rare autosomal recessive inherited disease with an overall clinical phenotype of failure to thrive, vomiting, severe dehydration, hyperkalemia, and hyponatremia. Mutations in the CYP11B2 gene encoding AS are responsible for the occurrence of ASD. Defects in CYP11B2 gene have only been reported in a limited number of cases worldwide. Due to this potential life-threatening risk, a comprehensive hormonal investigation followed by genetic confirmation is essential for the clinical management of offspring. We report a case of a newborn who was found to have persistent hyponatremia, hyperkalemia, low aldosterone level, raised renin levels, normal cortisol, and normal 17 hydroxyprogesterone level, suggesting the diagnosis of isolated ASD. Genetic report was suggestive of isolated ASD caused by a novel base pair deletion in exon 3, homozygous CYP11B2 variant (chr8:g.142915123_142915125del; depth: 124x d) (p.Lys175del; ENST00000323110.2). After initial steps of rehydration and salt restoration, the child was started on oral tablet fludrocortisone. The child responded well and showed a good gain in growth and development. We elaborate on the biochemical and genetic work-up performed and describe potential pitfalls in CYP11B2 sequencing due to its homology to CYP11B1.