Inherited forms of distal renal tubular acidosis. Characteristics in adulthood

Background. Distal renal tubular acidosis (dRTA) is characterized by defective urinary acidification resulting in impaired excretion of protons, ammonium and titratable acids. Subsequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are caused by mutations in three different genes, namely SLC4A1, ATP6V1 B1 and ATP6V0A4 where SLC4A 1 mutations mostly occur in an autosomal dominant manner and rarely as recessive mutations. The ATP6V1 B1 and ATP6V0A4 mutations each affect two different subunits of the vacuolar H+-ATPase proton pump, the B1 and a4 subunits and are inherited in an autosomal recessive manner. Clinical manifestations of dRTA usually occur during infancy or childhood. Heterozygous carriers of ATP6V1 B1 and ATP6V0A4 mutations may have a higher risk to develop nephrolithiasis and nephrocalcinosis, respectively. Results. Depending on the respective gene mutation patients may present with mild clinical symptoms, such as mild metabolic acidosis and incidental detection of kidney stones or severe manifestations, such as failure to thrive, severe metabolic acidosis and nephrocalcinosis. Progressive sensorineural hearing loss develops in the majority of patients with recessive dRTA (ATP6V1B1 and ATP6V0A4 mutations). Some patients with recessive dRTA may also develop abnormal widening of the vestibular aqueduct. Conclusion. Distal RTA is an important differential diagnosis in children as well as in young adults with nephrocalcinosis or recurrent kidney stone formation, particularly if stone composition consists of 100% apatite or if there is history of hearing abnormalities.