Pseudohypoaldosteronism in a newborn male with functional polymorphisms in the mineralocorticoid receptor genes
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초록
Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2-p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature.
Abstract
Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2-p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature.
참고문헌 (20)
- Cheek DB, "A salt wasting syndrome in infancy", Arch Dis Child, 33, pp.252~256 (1958)
- Zennaro MC., "Mineralocorticoid resistance", Steroids, 61, pp.189~192 (1996)
- Geller DS, "Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I", Nat Genet, 19, pp.279~281 (1998)
- Chang SS, "Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1", Nat Genet, 12, pp.248~253 (1996)
- Kwon YS, "A case of pseudohypoaldosteronism", J Korean Pediatr Soc, 35, pp.984~988 (1992)
- Lee JE, "Two cases of pseudohypoaldosteronism type I", J Korean Pediatr Soc, 37, pp.122~128 (1994)
- Lee R, "Two male siblings with pseudohypoaldosteronism type I", J Korean Pediatr Soc, 37, pp.262~268 (1994)
- Kang IN, "A case of pseudohypo aldosteronism", J Korean Pediatr Soc, 38, pp.1160~1163 (1995)
- Kim SJ, "Two cases with pseudohypoaldosteronism", J Korean Soc Pediatr Endocrinol, 5, pp.215~219 (2000)
- 최준기, "신우요관이행부폐색과 동반된 일과성 가성저알도스테론혈증 1례", Childhood Kidney Diseases, 8(1), pp.91~95 (2004), 대한소아신장학회
- 엄미령, "영아기 이후 진단 된 1형 가성 저알도스테론증 1례", Annals of Pediatirc Endocrinology & Metabolism, 12(1), pp.82~86 (2007), 대한소아내분비학회
- 안소윤, "Pseudohypoaldosteronism in a premature neonate with severe polyhydramnios in utero", Korean Journal of Pediatrics, 52(3), pp.376~379 (2009), 대한소아과학회
- Se Eun Lee, "A case of pseudohypoaldosteronism type 1 with a mutation in the mineralocorticoid receptor gene", Korean Journal of Pediatrics, 54(2), pp.90~93 (2011), 대한소아과학회
- Ahn HS., "Hong Chang Yee textbook of pediatrics", pp.1240~ (2012), Mirae N Co
- Riepe FG., "Pseudohypoaldosteronism", Endocr Dev, 24, pp.86~95 (2013)
- Amin N, "Pseudohypoaldosteronism type 1: clinical features and management in infancy", Endocrinol Diabetes Metab Case Rep, 2013, pp.130010~ (2013)
- Geller DS., "Mineralocorticoid resistance", Clin Endocrinol (Oxf), 62, pp.513~520 (2005)
- Arai K, "Functional polymorphisms in the mineralocorticoid receptor and amirolide-sensitive sodium channel genes in a patient with sporadic pseudohypoaldosteronism", Hum Genet, 112, pp.91~97 (2003)
- van Leeuwen N, "The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels", Hypertension, 56, pp.995~1002 (2010)
- Geller DS, "Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for neonatal lethality, and phenotypic expression in adults", J Am Soc Nephrol, 17, pp.1429~1436 (2006)