A further case of renal tubular dysgenesis surviving the neonatal period

Abstract

Renal tubular dysgenesis is a critical disorder characterized by the Potter phenotype and severe hypotension in the early neonatal period. We herein report a 3-year-old female with renal tubular dysgenesis. Endocrinological studies showed a high plasma renin activity (over 49.2 ng/ml/h; normal range 2.0-15.2), high active renin concentration (1,823.5 pg/ml; normal range 2.4-21.9), and low angiotensin-converting enzyme (ACE) concentration (1.7 U/l; normal range 8.3-21.4). Taken together, these findings suggested an abnormality of the ACE gene, ACE. Direct sequencing analysis revealed two novel deletions in the coding region of ACE. We conclude that hormonal analysis of the renin-angiotensin system can aid in identifying the responsible genes and help with efficient gene analysis and pathophysiological considerations.

Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

“…Mutations in the RAS genes are reported in 15 families [Bacchetta et al, 2007;Ben Amar et al, 2007;Danilov et al, 2010;Gribouval et al, 2005;Michaud et al, 2011;Schreiber et al, 2010;Uematsu et al, 2006Uematsu et al, , 2009Zingg-Schenk et al, 2008] and new sequence changes identified in our laboratory in 33 families are presented in Table 1. New mutations were identified by direct sequence analysis as described previously [Gribouval et al, 2005].…”

“…All except those previously reported in four families [Danilov et al, 2010;Gribouval et al, 2005;Schreiber et al, 2010;Uematsu et al, 2009] were novel. Mutations were present in the homozygous state in 15 families, in the compound heterozygous state in 13, whereas only one heterozygous ACE mutation was identified in three families.…”

“…Two patients survive, one belonging to family DYS 114 has chronic kidney disease at 3 years [Schreiber et al, 2010], the second, in family DYS 159, developed end stage renal disease (ESRD) and has been transplanted at the age of 3 years; her brother died at 3 days of life. The phenotype was also uniformly severe in cases with truncating ACE mutations, with ESRD requiring dialysis from birth (one case) [Uematsu et al, 2009], fetal (four cases) or early postnatal death (19 cases), or termination of pregnancy (three cases), whereas different patterns of evolution were observed in the five patients belonging to families with at least one nontruncating mutation.…”

“…Since the initial publication, nearly 100 cases of sporadic or familial cases of RTD have been reported [Allanson et al, 1992;Ariel et al, 1995;Bacchetta et al, 2007;Ben Amar et al, 2007;Bernstein and Barajas, 1994;Danilov et al, 2010;Gribouval et al, 2005;Huang et al, 2003;Kriegsmann et al, 2000;Kumar et al, 1997;Kumral et al, 2003;Lacoste et al, 2006;MacMahon et al, 1990;Mantan et al, 2004;McFadden et al, 1997;Metzman et al, 1993;Michaud et al, 2011;Milunsky et al, 1997;Moldavsky, 2009;Querfeld et al, 1996;Russo et al, 1991;Schreiber et al, 2010;Schwartz et al, 1986;Swinford et al, 1989;Uematsu et al, 2006Uematsu et al, , 2009Voland et al, 1985;Zingg-Schenk et al, 2008]. Renal lesions are more diffuse than initially described: Henle loops and collecting ducts are collapsed whereas the muscular wall of medium-sized arteries and arterioles is thickened and disorganized [Ariel et al, 1995;Lacoste et al, 2006;Voland et al, 1985].…”

Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts

“…Inherited RTD is caused by mutations in the genes encoding the components of the reninangiotensin system (RAS) [2]. Mutations in the genes encoding angiotensinogen (AGT), renin, angiotensinconverting enzyme (ACE), and angiotensin II receptor type 1 have been reported in several case reports [1,[3][4][5][6][7][8]. RTD is also associated with fetopathy induced by drugs such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs) [9][10][11].…”