| H00243 | |
| H number | H00243 |
| Name | Hyperkalemic distal renal tubular acidosis (RTA type 4) |
| Description | Renal tubular acidosis (RTA) is characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal impaired acid excretion. Type 4 RTA is a heterogeneous group of disorders associated with hyperkalemia due to aldosterone deficiency or impairment in aldosterone molecular signaling. Primary pseudohypoaldosteronism type 1 (PHA1) is characterized by salt-wasting, hyperkalemia, and metabolic acidosis in the presence of markedly elevated plasma renin activity and aldosterone concentration. In the autosomal dominant form, aldosterone resistance is due to heterozygous mutations in the mineralocorticoid receptor gene. In the autosomal recessive form, aldosterone resistance is caused by loss-of-function homozygous mutations in the genes encoding one of the three constitutive subunits (alpha, beta, and gamma) of the epithelial Na+ channel (SCNN1A, SCNN1B, and SCNN1G). Other inherited cause of type 4 RTA includes hyperkalaemia associated with hypertension and low or normal levels of plasma aldosterone. This syndrome is called pseudohypoaldosteronism type 2 (PHA2), or Gordon's syndrome, which results in a renal aldosterone resistance. Mutations in the genes encoding WNK1 and WNK4 kinases (WNK1 and WNK4), which regulate ion-transporters on renal tubules, were identified in patients with PHA2. Acquired hyperkalemic RTA is observed in the context of mineralocorticoid deficiency, systemic lupus erythematosus, and AIDS nephropathy. It is also often seen in a number of tubulointerstitial renal diseases. Finally, a great number of drugs may induce hyperkalemic RTA. |
| Category | Urinary system disease |
| Network | - |
| Gene | (PHA1A) NR3C2 [HSA:4306] [KO:K08555] (PHA1B1) SCNN1A [HSA:6337] [KO:K04824] (PHA1B2) SCNN1B [HSA:6338] [KO:K04825] (PHA1B3) SCNN1G [HSA:6340] [KO:K04827] (PHA2B) WNK4 [HSA:65266] [KO:K08867] (PHA2C) WNK1 [HSA:65125] [KO:K08867] (PHA2D) KLHL3 [HSA:26249] [KO:K10443] (PHA2E) CUL3 [HSA:8452] [KO:K03869] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | Sodium bicarbonate [DR:D01203] |
| Comment | - |
| Other DBs | ICD-11: GB90.44 ICD-10: N25.8 MeSH: D011546 OMIM: 177735 264350 620125 620126 145260 614491 614492 614495 614496 |
| Reference | PMID:19721811 AUTHORS Pereira PC, Miranda DM, Oliveira EA, Silva AC TITLE Molecular pathophysiology of renal tubular acidosis. JOURNAL Curr Genomics 10:51-9 (2009) DOI:10.2174/138920209787581262 PMID:11045400 AUTHORS Rodriguez-Soriano J TITLE New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies. JOURNAL Pediatr Nephrol 14:1121-36 (2000) DOI:10.1007/s004670000407 PMID:12138150 AUTHORS Rodriguez Soriano J TITLE Renal tubular acidosis: the clinical entity. JOURNAL J Am Soc Nephrol 13:2160-70 (2002) DOI:10.1097/01.ASN.0000023430.92674.E5 PMID:9662404 (PHA1A) AUTHORS Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP TITLE Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. JOURNAL Nat Genet 19:279-81 (1998) DOI:10.1038/966 PMID:8589714 (PHA1B1 PHA1B2) AUTHORS Chang SS, Grunder S, Hanukoglu A, Rosler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP TITLE Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. JOURNAL Nat Genet 12:248-53 (1996) DOI:10.1038/ng0396-248 PMID:8640238 (PHA1B3) AUTHORS Strautnieks SS, Thompson RJ, Gardiner RM, Chung E TITLE A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families. JOURNAL Nat Genet 13:248-50 (1996) DOI:10.1038/ng0696-248 PMID:11498583 (PHA2B PHA2C) AUTHORS Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP TITLE Human hypertension caused by mutations in WNK kinases. JOURNAL Science 293:1107-12 (2001) DOI:10.1126/science.1062844 PMID:22266938 (PHA2D PHA2E) AUTHORS Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, Semmekrot BA, Poujol A, Valimaki MJ, De Ferrari ME, Sanjad SA, Gutkin M, Karet FE, Tucci JR, Stockigt JR, Keppler-Noreuil KM, Porter CC, Anand SK, Whiteford ML, Davis ID, Dewar SB, Bettinelli A, Fadrowski JJ, Belsha CW, Hunley TE, Nelson RD, Trachtman H, Cole TR, Pinsk M, Bockenhauer D, Shenoy M, Vaidyanathan P, Foreman JW, Rasoulpour M, Thameem F, Al-Shahrouri HZ, Radhakrishnan J, Gharavi AG, Goilav B, Lifton RP TITLE Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities. JOURNAL Nature 482:98-102 (2012) DOI:10.1038/nature10814 |