Affected patients present with renal tubular acidosis, nephrocalcinosis, and renal failure. Hypokalemia with muscle weakness and periodic paralysis is frequent. Polyuria, vomiting, and dehydration lead to fluid and electrolyte imbalances.
Primary Distal Renal Tubular Acidosis (primary dRTA); Butler-Albright Syndrome; Lightwood-Butler-Albright Syndrome.
Unknown. Females are slightly more often affected.
Mainly autosomal dominant, but autosomal recessive and multiple dominant forms have also been described. However, the disorder most often occurs sporadically. Several genes are known to cause dRTA. Mutations in the ATP6V1B1 (ATPase, H+ transporting, lysosomal beta-polypeptide) and ATP6V0A4 genes encoding for subunits of the apical H+/ATPase pump located on chromosome 2 and 7, respectively, are most commonly affected in the autosomal recessive form of dRTA. Mutations in the SLC4A1 (solute carrier family 4) gene encoding the basolateral Cl-/HCO3- exchanger and located on chromosome 17 generally results in the autosomal dominant form of dRTA.
The primary defect is a diminished ability to excrete hydrogen ions as ammonium and titratable acid in the α-intercalated cell of distal renal tubule, despite a low-plasma bicarbonate concentration. The glomerular filtration rate is normal. Metabolic acidosis results from the inability to excrete the full endogenous load of nonvolatile acids (eg, phosphate, sulfate), while the generation of bicarbonate is minimal.
Fatigue, anorexia, vomiting, constipation, polyuria, dehydration, and growth retardation are the main symptoms. Nephrocalcinosis is an almost constant finding and may lead to interstitial nephropathy and renal failure. Affected patients are unable to achieve a urine pH below 5.5 and typical laboratory findings include hyperchloremic metabolic acidosis, hypokalemia, hypercalciuria, and hypocitraturia.
Children with autosomal recessive-inherited mutations often present in the first year of life, while children with autosomal dominant mutations tend to present after the first year of life. Failure to thrive and growth retardation are common and can be severe. Chronic metabolic acidosis is responsible for osteomalacia with pathologic fractures (secondary to decreased intestinal calcium resorption), and nephrocalcinosis with possible renal insufficiency. Hyperchloremia, hypokalemia, and low serum bicarbonate are responsible for polyuria (secondary nephrogenic diabetes insipidus). Hypokalemia may be severe enough to cause muscle weakness or even ☞periodic paralysis-like symptoms. Twenty-five percent of patients may present as a metabolic emergency. Life-threatening dehydration can be associated with flaccid paralysis, respiratory difficulties, cardiac arrhythmias, circulatory collapse, and coma. Medullary kidney cysts and sensorineural deafness have been described in some patients. Alkali therapy is used to provide an adequate amount of base to balance daily acid production. Children have a higher rate of acid production, thus require higher doses of alkali (up to 5-8 mEq/kg of citrate or HCO3) than adults (about 0.5-1 mEq/kg). ...