The carbonic anhydrase II (CAII) deficiency syndrome is a rare autosomal recessive osteopetrosis with renal tubular acidosis (RTA) and cerebral calcifications (MIM259730).
CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine and bicarbonaturia, consistent with a type III renal tubular acidosis.
By CNI dosage reduction or adding low dose fludrocortisone, or temporarily switching to SRL, the prognosis of CNI-induced hyperkalemic RTA is favourable.
The role of NOTCH2 and JAG1 in formation of proximal nephron structures and podocytes might explain the observed phenotypes of renal dysplasia and proteinuria in patients with Alagille syndrome, and renal tubular acidosis may be the result of JAG1 expression in the collecting ducts.
The hearing loss may thus be paralleled by various renal phenotypes including a subtle decrease of proximal Na(+)-coupled transport (KCNE1/KCNQ1), impaired K(+) secretion (KCNMA1), limited HCO(3)(-) elimination (SLC26A4), NaCl wasting (BSND and CLCNKB), renal tubular acidosis (ATP6V1B1, ATPV0A4, and KCC4), or impaired urinary concentration (CLCNKA).
The hearing loss may thus be paralleled by various renal phenotypes including a subtle decrease of proximal Na(+)-coupled transport (KCNE1/KCNQ1), impaired K(+) secretion (KCNMA1), limited HCO(3)(-) elimination (SLC26A4), NaCl wasting (BSND and CLCNKB), renal tubular acidosis (ATP6V1B1, ATPV0A4, and KCC4), or impaired urinary concentration (CLCNKA).
Hyperkalemic RTA accompanied by hypertension (pseudohypoaldosteronism type 2 [PHA2]) is caused by dominant gain-of-function mutations in the kinases WNK1 and WNK4.
Accordingly, KSHV upregulated the expression of RTA (Orf50), a master transactivator of KSHV lytic replication, and activated its promoter during primary infection.
By studying molecular mechanisms of human disease-causing missense mutations within <i>a</i> subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (<i>a</i>2) and ATP6V0A4 (<i>a</i>4) subunits and their mutants, <i>a</i>2<sup>P405L</sup> (causing cutis laxa), and <i>a</i>4<sup>R449H</sup> and <i>a</i>4<sup>G820R</sup> (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells.
Accordingly, KSHV upregulated the expression of RTA (Orf50), a master transactivator of KSHV lytic replication, and activated its promoter during primary infection.