The following summary is from Orphanet
, a European reference portal for information on rare diseases and orphan drugs.
Orpha Number: 18
Distal renal tubular acidosis (dRTA) is a disorder of impaired net acid secretion by the distal tubule characterized by hyperchloremic metabolic acidosis. The classic form is often associated with hypokalemia whereas other forms of acquired dRTA may be associated with hypokalemia, hyperkalemia or normokalemia.
Prevalence of dRTA is unknown but is often underreported. The hereditary forms of dRTA are more prevalent in areas of high consanguinity (Arabic peninsula and North Africa) whereas acquired dRTA has been reported more frequently in Western countries.
Disease onset can occur at any age, depending on cause. Hereditary dRTA subtypes include autosomal dominant (AD) and autosomal recessive (AR) dRTA (see these terms). A recessive subtype of dRTA associated with anemia has also been described in Southeast Asia. AR forms are frequently diagnosed in infants and young children. AD dRTA is mostly diagnosed in adolescents and young adults. Patients with dRTA can be asymptomatic or can present with polyuria, polydipsia, weakness and fatigue (symptoms associated with hypokalemia). Failure to thrive, rickets, stunting of growth (seen in children) and osteomalacia or osteopenia (seen in adults) are a result of urinary calcium wastage and a loss of calcium salts from the bones. Hypercalciuria, nephrolithiasis and nephrocalcinosis usually occur. Low plasma potassium levels in those with the classic form of dRTA can also cause cardiac arrhythmias, paralysis and even death. In the recessive forms of dRTA, progressive and irreversible deafness often occurs.
dRTA can be acquired or inherited. AD dRTA is usually due to mutations in the SLC4A1 gene (17q21.31). Mutations in the ATP6V1B1 gene (2p13) or ATP6V0A4 gene (7q34) are responsible for AR dRTA with deafness. AR dRTA without deafness or late onset deafness has been mainly described in patients with mutations in the ATP6V0A4 gene but overlap does exist in that some patients with this mutation develop deafness and others do not. Acquired forms of dRTA are thought to be caused by autoimmune diseases such as Sjögren syndrome (see this term) or secondary to other conditions like sickle cell anemia, systemic lupus erythematosus (see these terms), chronic obstructive uropathy, or post-renal transplantation.
The disease is characterized by hyperchloremic metabolic acidosis. The inability to lower urine pH below 5.5 and a positive urine anion gap during spontaneous metabolic acidosis is indicative of dRTA. Provocative tests for further diagnosis include the NH4Cl acidifying test and the furosemide test. Patients with dRTA also show renal potassium wasting except in the hyperkalemic type of dRTA. Molecular genetic testing for one of the causal genetic mutations can also confirm diagnosis.
The main differential diagnosis is proximal RTA (see this term) along with other causes of chronic metabolic acidosis (i.e. diarrhea).
Antenatal diagnosis is rarely performed.
The inherited forms of dRTA are inherited autosomal dominantly or recessively and genetic counseling is possible.
Management and treatment
Alkali therapy is the standard treatment (to achieve normal serum bicarbonate levels). Patients are usually given sodium bicarbonate or sodium citrate. Children require very high doses (4-8 meq/kg/day) whereas adults need much lower doses (1-2 meq/kg/day). Potassium replacement is also necessary in hypokalemic patients and potassium citrate is usually recommended. The dose depends on the severity of hypokalemia. Hyperkalemic types require low dietary potassium intake and other therapies.
All forms of dRTA are chronic and may have significant effects on growth and development. With treatment there is no decrease in life expectancy and renal failure is uncommon but progressive chronic kidney disease may sometimes occur if there are recurrent kidney stones and when nephrocalcinosis is very severe.
Last updated: 4/22/2014