Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin Converting Enzyme Inhibitors (ACE-I) have been very effective in treating hypertension. Adverse conditions in the fetus with the use of ACE-I, such as oligohydramnios, intra-uterine growth restriction (IUGR), hypocalvaria, persistent ductus arteriosus with fetal and neonatal death have been rerported. Though the pathophysiology was thought to be a problem with renal hypoperfusion in the fetus, it remained unclear whether the first trimester exposure to these drugs produced a similar pattern. We participated in a collaborative trial initiated by the Organization of Teratology Information Services (OTIS) in the United States to examine whether first trimester exposure to ACE-I was of concern. Eight women from our High Risk Pregnancy Unit who delivered in our hospital were enrolled in the trial. All were treated with either Enalapril or Captopril in the first trimester due to various reasons, mainly chronic hypertension and diabetic nephropathy. No major malformations were detected in the nine newborns studied (one pair of twins). Two cases of IUGR were diagnosed, one of them ended in an intra-uterine death, but this was attributed to maternal severe disease and probably not to drug effect. We are definitely not suggesting that women should stay on ACE-I until the second trimester, but it seems that renal blood flow and its associated problems with glomerular filtration are not affected in the first trimester.
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PMID:Angiotensin converting enzyme inhibitors use in the first trimester of pregnancy. 2351 Dec 71

Renal tubular dysgenesis is a severe disease characterized by the absence of differentiated proximal tubules, leading to fetal anuria and persistent oligohydramnios. The absence of amniotic fluid results in a series of malformations, including facial dysmorphia, limb deformation and also lung hypoplasia, leading to respiratory distress at birth. The disease is linked to mutations in the AGT, REN ACE andAGTR1 genes that compose the renin-angiotensin system (RAS). The absence of functional RAS leads to fetal and neonatal hypotension, renal hypoperfusion, and tubular dysgenesis. The use of cellular models expressing these mutations has advanced our understanding of the structure-function relationship of RAS proteins, notably by showing that defective misfolded proteins undergo either intracellular accumulation and retention, or rapid degradation. Moreover, these studies confirm that ACE has to be inserted in the plasma membrane to be active.
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PMID:[Renal tubular dysgenesis and mutations in the renin-angiotensin system genes]. 2626 8

Background. Late pregnancy usage of angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) may cause severe oligohydramnios due to fetal renal impairment. Affected neonates will often suffer from fatal, renal, and respiratory failure. Case. A 39-year-old multigravida admitted due to anhydramnios secondary to valsartan (ARB) exposure at 30 weeks' gestation. Following secession of treatment amniotic fluid volume returned to normal. Delivery was induced at 34 weeks' gestation following premature rupture of membranes and maternal fever. During the two-year follow-up, no signs of renal insufficiency were noted. Conclusions. This description of reversible fetal renal damage due to ARB intake during pregnancy is the first to show no adverse renal function in a two-year follow-up period. This case may help clinicians counsel patients with pregnancies complicated by exposure to these drugs.
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PMID:Reversible Fetal Renal Impairment following Angiotensin Receptor Blocking Treatment during Third Trimester of Pregnancy: Case Report and Review of the Literature. 2767 62

Autosomal recessive renal tubular dysgenesis (RTD) is a rare lethal disease affecting renal development before birth. RTD is manifested by anuria and severe hypotension resulting in oligohydramnios and birth defects known as Potter's syndrome. Homozygous or compound heterozygous mutations in genes encoding components of the renin-angiotensin system (ACE, AGT, AGTR1 and REN) have been reported to cause RTD. A consanguineous family with a history of multiple stillbirths was investigated using prenatal ultrasound and molecular genetic analysis of an affected foetus. Prenatal ultrasound scan suggested RTD, and a novel homozygous frameshift mutation c.299_300delAA (p.Lys100Serfs*4) in the REN gene was identified by whole-exome sequencing, which segregated with parental DNA samples. RTD remains a rare but important cause of prenatal and perinatal death and may present with antenatally hyperechogenic kidneys.
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PMID:Renal tubular dysgenesis: antenatal ultrasound scanning and molecular investigations in a Saudi Arabian family. 2799 58

We report a 32-week fetus conceived of consanguineous parentage which presented with severe early onset oligohydramnios and history of a similarly affected sibling in previous pregnancy. Ultrasonography and autopsy were inconclusive, prompting exome sequencing on fetal DNA. This resulted in identification of a homozygous novel 3' splice-site variation in intron 17 of the ACE gene (NM_000789.3:c.2642-1G>A), confirming diagnosis of autosomal recessive renal tubular dysgenesis, and facilitating prenatal diagnosis in subsequent pregnancy.
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PMID:Exome sequencing identifies novel ACE splice-site variant in a fetus with renal tubular dysgenesis. 3005 38

Renal tubular dysgenesis (RTD) is a rare fatal disorder in which there is poor development of proximal tubules, leading to oligohydramnios and the Potter sequences. RTD occurs secondary to renin-angiotensin system (RAS) blockade during the early stages of fetal development or due to autosomal recessive mutation of genes in the RAS pathway. A boy born at 33+1 weeks due to cord prolapse was found to be anuric and hypotensive. Pregnancy was complicated by severe oligohydramnios from gestational age 28+4 weeks. Abdominal sonography revealed diffuse globular enlargement of both kidneys with increased cortical parenchymal echogenicity. Infantogram showed a narrow thoracic cage and skull X-ray showed large fontanelles and wide sutures suggestive of ossification delay. Basal plasma renin activity was markedly elevated and angiotensin-converting enzyme was undetectable. Despite adequate use of medications, peritoneal dialysis, and respiratory support, he did not recover and expired on the 23rd day of life. At first, autosomal recessive polycystic kidney disease was suspected, but severe oligohydramnios along with refractory hypotension, anuria, skull ossification delay and high renin levels made RTD suspicious. ACE gene analysis revealed compound heterozygous pathogenic variations of c.1454.dupC in exon 9 and c.2141dupA in exon 14, confirming RTD. Based on our findings, we propose that, although rare, RTD should be suspected in patients with severe oligohydramnios and refractory hypotension.
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PMID:A Premature Baby with Severe Oligohydramnios and Hypotension: a Case Report of Renal Tubular Dysgenesis. 3280 12


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