Familial Autosomal Recessive Renal Tubular Acidosis: Importance of Early Diagnosis

Abstract

Background and Aims: Untreated renal tubular acidosis (RTA) can result in severe complications. We reviewed the clinical features of patients with mutations in two genes causing RTA and evaluated their developmental expression assuming that timing, symptom severity and complications may be related to its occurrence. Methods: Clinical data from 16 patients with RTA due to mutations in either ATP6V1B1 or CAII were retrospectively reviewed. Both genes’ localization and expression pattern in the developing human kidney were analyzed by real-time polymerase chain reaction and immunostaining. Results: RTA-presenting symptoms were non-specific. Patients with mutations in ATP6V1B1 had earlier presentation (4.9 vs. 11 months, p < 0.041) and longer time to diagnosis than patients with CAII mutations (5.8 vs. 57 months, p < 0.01). Patients with ATP6V1B1 mutations were more likely to develop chronic kidney disease than those with CAII mutations (follow-up GFR values: 89 vs. 110 ml/min/1.73 m², respectively, p < 0.017), probably secondary to nephrocalcinosis. Both ATP6V1B1 and CAII were expressed early during human nephrogenesis, with relatively higher transcript levels of ATP6V1B1. Conclusions: There is considerable delay in establishing a diagnosis of both types of RTA, supporting the need for earlier biochemical investigation. RTA due to ATP6V1B1 mutations is associated with mild progressive loss of kidney function.

Inherited secondary nephrogenic diabetes insipidus: concentrating on humans

“…Another inherited disorder associated with hypokalemia and hypercalciuria is distal renal tubular acidosis (dRTA). Several genes are known to cause dRTA, which all affect the ability of intercalated cells in the collecting duct to secrete protons (35,65). Again, polyuria/ polydipsia is a common symptom of this disease, and there are some case reports documenting associated NDI (10, 23), but no systematic data collection of urinary concentrating ability in these patients exists.…”

Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

“…In some cases, NC provides a clue to an underlying genetic disorder such as hyperoxaluria or distal renal tubular acidosis with or without deafness [2, 3]. In other cases, NC is a side effect of chronic treatment with various drugs, including loop diuretics and vitamin D. In general, the pathogenesis of NC has not been adequately elucidated, although hypercalciuria appears to be a common finding.…”

Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss

“…The p.Pro346Arg mutation was previously detected in one patient among 62 studied kindreds of Turkish, Spanish, Saudi Arabian, North American, Pakistani, and European origin (5). A recent study found this mutation in patients from various ethnic groups suggesting to be a common pan‐ethnic mutation (14).…”

“…Mutations in ATP6V1B1 gene cause dRTA with or without SNHL (Table S3) (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The majority of these mutations are missense or nonsense mutations.…”