DISEASE: Hyperkalemic distal renal tubular acidosis (RTA type 4)
Entry
H00243 Disease
Name
Hyperkalemic distal renal tubular acidosis (RTA type 4)
Subgroup
Pseudohypoaldosteronism type I (PHA1) Pseudohypoaldosteronism type II (PHA2) Gordon syndrome
Supergrp
High blood pressure [DS:H01633] Renal tubular acidosis [DS:H02310]
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
Brite
Human diseases in ICD-11 classification [BR:br08403]
16 Diseases of the genitourinary system
Diseases of the urinary system
GB90 Certain specified disorders of kidney or ureter
H00243 Hyperkalemic distal renal tubular acidosis (RTA type 4)
Pathway-based classification of diseases [BR:br08402]
Endocrine system
nt06325 Hormone/cytokine signaling
H00243 Hyperkalemic distal renal tubular acidosis (RTA type 4)
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.
