Clinical analysis of salt-wasting in infants due to genetic aetiology
Abstract
Introduction: This study was aimed to get an overview of the clinical analyses and genetic characteristics of salt-wasting (SW) in infants caused by genetic aetiology.
Material and methods: A retrospective study was conducted for infants at the Paediatric Unit of the First Affiliated Hospital of Guangxi Medical University from January 2012 to July 2022.
Results: Thirty infants were enrolled in this retrospective study. Twenty-six infants (86.7%) were diagnosed with congenital adrenal hyperplasia (CAH), and all of them had SW type 21-hydroxylase deficiency. Four infants (13.3%) were non-CAH. One girl was diagnosed with congenital chloride diarrhoea due to known homozygous mutations in the SLC26A3 gene, and another girl had Barter’s syndrome due to a mutation in the CLCNKB gene. One boy was diagnosed with pseudohypoaldosteronism type 1 due to a novel mutation in the NR3C2 gene, and another boy was confirmed with aldosterone synthase deficiency due to novel compound heterozygous mutations in the CYP11B2 gene. Meanwhile, we verified the pathogenicity of the novel compound heterozygous of CYP11B2 gene in in vitro experiments.
Conclusions: The genetic aetiologies of infants with SW were mostly CAH. However, pseudohypoaldosteronism and aldosterone synthase deficiency should also be considered in infants who present with salt-wasting syndrome. Normal or high aldosterone levels cannot be a factor by which to rule out the possibility of aldosterone synthase deficiency (ASD) in infancy. Gene analysis can be used to confirm
the disorder.
Keywords: salt wastinginfantcongenital adrenal hyperplasiaaldosterone synthase deficiencypseudohypoaldosteronism
References
- Bockenhauer D, Zieg J. Electrolyte disorders. Clin Perinatol. 2014; 41(3): 575–590.
- Davids MR, Edoute Y, Jungas RL, et al. Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments. Can J Physiol Pharmacol. 2002; 80(9): 835–850.
- Bizzarri C, Pedicelli S, Cappa M, et al. Water Balance and 'Salt Wasting' in the First Year of Life: The Role of Aldosterone-Signaling Defects. Horm Res Paediatr. 2016; 86(3): 143–153.
- Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011; 32(1): 81–151.
- Wijaya M, Ma H, Zhang J, et al. Aldosterone signaling defect in young infants: single-center report and review. BMC Endocr Disord. 2021; 21(1): 149.
- Bizzarri C, Olivini N, Pedicelli S, et al. Congenital primary adrenal insufficiency and selective aldosterone defects presenting as salt-wasting in infancy: a single center 10-year experience. Ital J Pediatr. 2016; 42(1): 73.
- Riepe FG. Clinical and molecular features of type 1 pseudohypoaldosteronism. Horm Res. 2009; 72(1): 1–9.
- Perez-Brayfield MR, Gatti J, Smith E, et al. Pseudohypoaldosteronism associated with ureterocele and upper pole moiety obstruction. Urology. 2001; 57(6): 1178.
- Dolezel Z, Starha J, Novotna D, et al. Secondary pseudohypoaldosteronism in an infant with pyelonephritis. Bratisl Lek Listy. 2004; 105(12): 435–437.
- Maruyama K, Watanabe H, Onigata K. Reversible secondary pseudohypoaldosteronism due to pyelonephritis. Pediatr Nephrol. 2002; 17(12): 1069–1070.
- White PC. Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol. 2004; 217(1-2): 81–87.
- Løvås K, McFarlane I, Nguyen HH, et al. A novel CYP11B2 gene mutation in an Asian family with aldosterone synthase deficiency. J Clin Endocrinol Metab. 2009; 94(3): 914–919.
- Nguyen HH, Hannemann F, Hartmann MF, et al. Aldosterone synthase deficiency caused by a homozygous L451F mutation in the CYP11B2 gene. Mol Genet Metab. 2008; 93(4): 458–467.
- Peter M, Nikischin W, Heinz-Erian P, et al. Homozygous deletion of arginine-173 in the CYP11B2 gene in a girl with congenital hypoaldosteronism. Corticosterone methyloxidase deficiency type II. Horm Res. 1998; 50(4): 222–225.
- Miao H, Yu Z, Lu L, et al. Analysis of novel heterozygous mutations in the CYP11B2 gene causing congenital aldosterone synthase deficiency and literature review. Steroids. 2019; 150: 108448.
- Perry R, Kecha O, Paquette J, et al. Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab. 2005; 90(6): 3243–3250.
- Chang Z, Lu W, Zhao Z, et al. Genetic aetiology of primary adrenal insufficiency in Chinese children. BMC Med Genomics. 2021; 14(1): 172.
- Speiser PW, Arlt W, Auchus RJ, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018; 103(11): 4043–4088.
- Miller WL. Mechanisms in endocrinology: Rare defects in adrenal steroidogenesis. Eur J Endocrinol. 2018; 179(3): R125–R141.
- Goda T, Komatsu H, Nozu K, et al. An infantile case of pseudohypoaldosteronism type 1 (PHA1) caused by a novel mutation of . Clin Pediatr Endocrinol. 2020; 29(3): 127–130.
- Turan I, Kotan LD, Tastan M, et al. Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance. Clin Endocrinol (Oxf). 2018; 88(6): 799–805.
- Root AW. Disorders of aldosterone synthesis, secretion, and cellular function. Curr Opin Pediatr. 2014; 26(4): 480–486.
- Merakou C, Fylaktou I, Sertedaki A, et al. Molecular Analysis of the CYP11B2 Gene in 62 Patients with Hypoaldosteronism Due to Aldosterone Synthase Deficiency. J Clin Endocrinol Metab. 2021; 106(1): e182–e191.
- Leshinsky-Silver E, Landau Z, Unlubay S, et al. Congenital hyperreninemic hypoaldosteronism in Israel: sequence analysis of CYP11B2 gene. Horm Res. 2006; 66(2): 73–78.
- Drop SL, Frohn-Mulder IM, Visser HK, et al. The effect of ACTH stimulation on plasma steroids in two patients with congenital hypoaldosteronism and in their relatives. Acta Endocrinol (Copenh). 1982; 99(2): 245–250.
- Williams TA, Mulatero P, Bosio M, et al. A particular phenotype in a girl with aldosterone synthase deficiency. J Clin Endocrinol Metab. 2004; 89(7): 3168–3172.
- Li N, Li J, Ding Yu, et al. Novel mutations in the CYP11B2 gene causing aldosterone synthase deficiency. Mol Med Rep. 2016; 13(4): 3127–3132.
- Hui E, Yeung MCw, Cheung PTo, et al. The clinical significance of aldosterone synthase deficiency: report of a novel mutation in the CYP11B2 gene. BMC Endocr Disord. 2014; 14: 29.
- Peterson JA, Graham SE. A close family resemblance: the importance of structure in understanding cytochromes P450. Structure. 1998; 6(9): 1079–1085.
- Martín-Rivada Á, Argente J, Martos-Moreno GÁ. Aldosterone deficiency with a hormone profile mimicking pseudohypoaldosteronism. J Pediatr Endocrinol Metab. 2020; 33(11): 1501–1505.
- Kuhnle U, Rösler A, Pareira JA, et al. The effects of long-term normalization of sodium balance on linear growth in disorders with aldosterone deficiency. Acta Endocrinol (Copenh). 1983; 102(4): 577–582.
- Gurpinar Tosun B, Kendir Demirkol Y, Seven Menevse T, et al. Catch-up Growth and Discontinuation of Fludrocortisone Treatment in Aldosterone Synthase Deficiency. J Clin Endocrinol Metab. 2022; 107(1): e106–e117.