| [ Summary ] |
Renal tubular acidosis (RTA) is one of the major causes of metabolic acidosis, often accompanied with bone and mineral disorders. Primary RTA is caused by genetic disorders. It is rare but quite important in terms of analyses of these diseases. Its elucidation has brought about breakthroughs in the explanation of tubular function, especially on the transporters and channels. In proximal tubule, mutations in Na+/HCO3- cotransporter (NBCe1) can cause autosomal recessive proximal RTA, accompanied with growth retardation, band keratopathy, intracranial calcification, etc. An X-linked recessive disorder, Dent's disease, accompanied with Fanconi syndrome (generalized proximal tubular dysfunction), rickets and growth retardation, has been proven to be linked to disorders in a chloride channel ClC-5. Disorders in vacuolar type H+ pump ATPase (V-ATPase) can cause distal RTA, often accompanied with hearing loss, growth retardation, renal and urinary tract calcification, etc. Genetically modified mouse models of the B1 subunit of V-ATPase have been shown to be associated with mild proximal RTA. Disorders in with-no-lysine kinase (WNK) variants and their related factors have been shown to cause pseudohypoaldosteronism type II, accompanied with mild distal RTA. These genetic RTA is thought to be needed essentially with genetic therapy. |