Background: Aldosterone synthase deficiency (ASD) is caused by biallelic inactivating CYP11B2 variants. Infants mainly present with failure to thrive and salt wasting in early infancy. Moreover, different factors may cause downregulation of aldosterone synthase and secondary deficiency.
Objective and Hypotheses: We present a toddler with polyuria and polydipsia and steroid hormone precursors suggestive of ASD, but normal CYP11B2 sequencing. We discuss differential diagnoses of ASD.
Case: A 1.5-year-old German boy was admitted with a first non-febrile status epilepticus due to hyponatremia (119 mmol/l). His previous history was uneventful. He was born at term (weight at birth 3580 g, 52 cm), did not show any problems in neonatal age or infancy, had thrived well, without vomiting, and reached developmental milestones adequately. However, parents had noted polyuria and polydipsia (at time of presentation > 2000 ml/d) since early infancy. After a short period of reduced fluid intake during intercurrent illness, he presented with marked hyponatremia of 119 mmol/l with normokalemia (4.4 mmol/l), but no signs of severe dehydration in clinical examination or blood gas analysis (pH 7.29, pCo2 52 mmHg, BE -2 mmol/l). With calculated infusion therapy, his status rapidly improved. Meningitis, infection and heart disease were ruled out and cerebral MRI was normal, there was no sign of SIADH. Aldosterone was detectable in hyponatremia, but inadequately low considering the context of severe hyponatremia. After normalization of sodium, an ACTH stimulation test was performed: Cortisol responded adequately and CAH was ruled out. Interestingly, corticosterone and 11-desoxycorticosterone showed an exaggerated response while aldosterone, being very low at baseline, did not show any relevant increment, suggesting a deficiency in terminal steps of aldosterone synthesis. Genetically, the diagnosis of ASD could not be confirmed. We only detected a heterozygous common variant in the coding sequence of the CYP11B2 gene. As a differential diagnosis, besides putative intronic or regulatory mutations, other factors besides the CYP11B2 gene may influence aldosterone production. With fludrocortisone treatment (0.1 mg/day) the boy continued to thrive, however, polydipsia remained.
Conclusion: ASD is an important differential diagnosis in isolated hyponatremia in toddlers. However, differential diagnosis can be challenging when diagnosis cannot be confirmed genetically.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology