Key result
Among 187 infants presenting with salt wasting, 90.4% were diagnosed with congenital adrenal hyperplasia, while 9.6% had non-CAH etiologies including aldosterone synthase deficiency and pseudohypoaldosteronism.
Why the study?
Aldosterone defects causing salt wasting are rare with mostly sporadic reported cases, warranting an overview of the etiology and clinical picture.
Observational (n=187)
No
In infants presenting with salt wasting, congenital adrenal hyperplasia is the most common etiology, but rare genetic defects in aldosterone synthesis or function must be considered, and normal plasma aldosterone does not rule out insufficiency.
Supports considering non-CAH etiologies in salt-wasting infants; hypothesis-generating for diagnostic algorithms.
BACKGROUND: Aldosterone (Ald) is a crucial factor in maintaining electrolyte and water homeostasis. Defect in either its synthesis or function causes salt wasting (SW) manifestation. This disease group is rare, while most reported cases are sporadic. This study aimed to obtain an overview of the etiology and clinical picture of patients with the above condition and report our rare cases. METHODS: A combination of retrospective review and case studies was conducted at the Pediatric Endocrine unit of The First Affiliated Hospital Sun Yat Sen University from September 1989 to June 2020. RESULTS: A total of 187 patients with SW were enrolled, of which 90.4% (n = 169) were diagnosed with congenital adrenal hyperplasia (CAH). SW type 21-hydroxylase deficiency accounted for 98.8% (n = 167) of CAH diagnosis, while 1.2% (n = 2) was of lipoid CAH. Non-CAH comprised 9.6% (n = 18) of the total patients whose etiologies included SF-1 gene mutation (n = 1), X-linked adrenal hypoplasia congenita (n = 9), aldosterone synthase deficiency (ASD, n = 4), and pseudo-hypoaldosteronism type 1 (PHA1, n = 1). Etiologies were not identified in three patients. All of patients with ASD and PHA1 exhibited SW syndrome in their early neonatal period. DNA sequencing showed mutations of CYP11B2 for P1-P4 and NR3C2 for P5. P1 and P2 were sibling brothers affected by compound heterozygous mutations of c.1121G > A (p.R374Q) and c.1486delC p.(L496fs); likewise, P4 was identified with compound heterozygous mutations of c.1200 + 1G > A and c.240-1 G > T; meanwhile P3 demonstrated c.1303G > A p.(G435S) homozygous mutation in CYP11B2 gene. Lastly, P5 showed c.1768 C > T p.(R590*) heterozygous mutation in the NR3C2 gene. CONCLUSION: Etiology of infant with aldosterone defect was mostly congenital. Renal and adrenal imaging are recommended to exclude renal causes. If clinical picture is suggestive, normal plasma Ald in early infancy cannot rule out aldosterone insufficiency.
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Wijaya et al. (2021) conducted an observational in Salt wasting due to aldosterone signaling defect (n=187). Aldosterone signaling defects was evaluated on Etiology of salt wasting. Among 187 infants presenting with salt wasting, 90.4% were diagnosed with congenital adrenal hyperplasia, while 9.6% had non-CAH etiologies including aldosterone synthase deficiency and pseudohypoaldosteronism.
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