The primary hereditary form of distal renal tubular acidosis : clinical and genetic studies in 60-member kindred

A distal (type 1) renal tubular acidosis (RTA-1) has been studied in 60 of 69 living members of a large family “HK” and two unrelated small families. The “HK” family, including 28 RTA-1 subjects, presents the first large family with only primary RTA-1 reported to date. The genetic situation in this family confirms the autosomal dominant transmission of the hereditary primary RTA-1 suggested previously on the basis of a few small families. Our data show that, in contrast to the secondary hereditary form, RTA-1 in its primary hereditary form is always complete and often tolerated (asymptomatic). It occurs in non-hypercalciuric families with no clinical variants observed in family members without RTA-1. In our series some clinical abnormalities commonly associated with RTA-1, such as nephrocalcinosis and growth retardation, appeared only in three cases among offspring when both parents were affected. The appearance of such abnormalities, taken as consequences of chronic acidosis in RTA-1, could be favored by the genetic background and/or the homozygosity for the RTA-1 gene. Linkage studies between RTA-1 and 10 genetic markers have been carried out. Results show that only ABO, MNS, GM and RH loci are informative for linkage analysis and none of these loci can be suggested as linked to RTA-1 locus.