Distal RTA with nerve deafness: clinical spectrum and mutational analysis in five children

Abstract

Distal renal tubular acidosis (RTA) with nerve deafness is caused by mutations in the ATP6V1B1 gene causing defective function of the H+ -ATPase proton pump. We report five acidotic children (four males) from four unrelated families: blood pH 7.21-7.33, serum bicarbonate 10.8-14.7 mEq/l, minimum urinary pH 6.5-7.1 and fractional excretion of bicarbonate in the presence of normal bicarbonatemia 1.1-5.7%. Growth retardation and nephrocalcinosis, but not hypercalciuria, were common presenting manifestations. Hearing was normally preserved in one of the patients whose sister was severely deaf. One child was homozygous for a known mutation in exon 1: C>T (R31X). Three children were homozygous for a splicing mutation, intron 6 + 1G>A. The other patient was a compound heterozygote, having this mutation and a previously unreported mutation in exon 10: G>A (E330K). Our report shows that hearing loss is not always present in the syndrome of distal renal tubular acidosis with nerve deafness and the absence of hypercalciuria at diagnosis and describes a new mutation responsible for the disease in the ATP6V1B1 gene.

Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis

“…In fact, normocalciuria is not uncommon at diagnosis in young dRTA patients (51 year). 4,14,15 As we all know, many factors can contribute to the differences in urinary calcium excretion, such as dietary, calcium absorption and hormonal control, as well as renal handling of calcium. Three (patient I-1, II-1 and IV-1) of the four patients with normocalciuria had evident signs of dehydration resulted by vomiting, fever, or other causes at diagnosis in this study.…”

“…The coding region and adjacent intronic segments of the ATP6V1B1 and SLC4A1 genes were amplified using of previously described primer pairs, respectively. 2,14 PCRs were performed in 50 lL of solution containing 0.2 mM dNTP, 0.03 U/lL Taq polymerase (Takara EX Taq Hot start version, DRR006B, Osaka, Japan), 2.0 mM MgCl 2 , 2.5 lL 10 Â PCR Mg 2+ -free buffer (Takara), approximately 50 ng genomic DNA and 1 mM of each primer. PCR was performed with an initial denaturation step at 95 C for 5 min, subsequently followed by 33 cycles with denaturation at 95 C for 45 s, annealing at 52-66 C for 45 s and elongation at 72 C for 45 s. PCR samples were subjected to bidirectional sequencing.…”

Familial Autosomal Recessive Renal Tubular Acidosis: Importance of Early Diagnosis

“…Patient’s genetic data and previously published mutations [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30] are presented in table 2. A mutation in CAII (c.583G>C, patient 4) that had never been reported before was found among them.…”

“…One possible mechanism may be related to their increased tendency to develop nephrocalcinosis complicated by renal stone disease [32]. We and others [21] clearly demonstrated that this group is prone to nephrocalcinosis compared to the CAII group. Nephrocalcinosis can impair tubular function by mechanical blockage of tubular fluid flow, followed by tubular atrophy, interstitial inflammation and interstitial fibrosis, and lead to the development of chronic kidney disease [33].…”

Clinical and laboratory approaches in the diagnosis of renal tubular acidosis

“…Table 1 summarizes the genetic and molecular basis, as well as the clinical, biochemical, and radiological findings useful to identify the subtype of RTA [1][2][3][4][5][6][7][8][9][10][11][12]. Information on acquired forms of RTA secondary to drugs and toxins or associated to systemic diseases is not included because this review mostly deals with congenital primary types of RTA, which are more frequently found in pediatric patients.…”