Atypical presentation of distal renal tubular acidosis in two siblings

Abstract

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.

Renal Fanconi syndrome in distal renal tubular acidosis

“…Renal proximal tubular dysfunction in untreated patients with dRTA has also been reported previously [1,2]. Although the precise pathogenic mechanism underlying development of this condition remains unclear, it has been suggested that hypokalemic nephropathy and defective V-ATPase resulting in impaired endosomal acidification may be involved [1,2].…”

“…Although the precise pathogenic mechanism underlying development of this condition remains unclear, it has been suggested that hypokalemic nephropathy and defective V-ATPase resulting in impaired endosomal acidification may be involved [1,2]. However, because the B1 subunit of VATPase is not expressed in renal proximal tubular cells, defective V-ATPase is unlikely to cause renal proximal tubular dysfunction in dRTA patients with the ATPV1B1 mutation [2].…”

Failure to thrive and nephrolithiasis in a boy with congenital cyanotic heart anomaly: answers

“…These proximal tubular abnormalities were transitory and resolved with alkali therapy. Transitory proximal renal tubular dysfunction may be associated with distal RTA [2][3][4].…”

“…However, following oral alkali therapy, all these abnormalities normalized. Watanabe [2] and our group [3] have previously described transitory proximal tubular dysfunction in children with distal RTA. The most likely mechanism for proximal tubular dysfunction is long-lasting hypokalemia.…”

Hypokalemic rhabdomyolysis in congenital tubular disorders: a case series and a systematic review

“…Pertinent secondary references were also considered. Using this research technique, we were able to accumulate 9 cases (5 male and 4 female subjects, ranging in age between 4.0 and 46, median 21 years) of congenital renal tubular disorders complicated by hypokalemic rhabdomyolysis that have been published in peer-reviewed English-language scientific journals [11][12][13][14][15][16][17][18][19] between 1983 and 2008. One patient who was reported twice in the literature was considered only once [12,13].…”