autosomal - recessive renal tubular dysgenesis ( ar - rtd ) is a rare inherited disorder caused by mutations in the genes encoding any of the components of the renin 
angiotensin system ( ras ) including renin , angiotensinogen , angiotensin - converting enzyme ( ace ) and type 1 angiotensin ii receptor .
fetuses may die in utero , and most neonates die soon after birth with persistent anuria , respiratory failure and refractory hypotension .
the histopathological hallmark of the disease is the absence or incomplete development of cortical convoluted proximal tubules [ 2 , 3 ] . since this disease was first described by allanson et al .   in 1983 , > 100 cases of rtd with or without genetic defects have been reported .
while most previous reports have described ar - rtd as a lethal disease , five recent cases have reportedly survived the neonatal period [ 58 ] . here , we report another case of ar - rtd associated with ace mutations who survived for over 2 years .
the first and second pregnancies were uneventful but the third pregnancy was complicated by anhydramnios and was terminated at 28 weeks of gestation .
the patient was born at 32 weeks and 4 days of gestation due to pre - term labor .
the weight was 1960 g ( 1050th percentile ) and the height was 41.5 cm ( 1050th percentile ) .
the baby required assisted ventilation immediately after birth due to respiratory distress , and inotropes were started at 1 h after birth due to hypotension .
the patient developed a pneumoperitoneum due to ileal perforation at 7 h after birth and he underwent emergency ileostomy .
hypotension was aggravated after surgery and the patient responded poorly to plasma expanders and inotropes .
while urination began to increase since day 4 , hypotension persisted and was even aggravated by diuresis . since day 25 , his blood pressure became relatively stable , and inotropes were tapered off for 2 weeks .
the peak serum creatinine level was 2.2 mg / dl ( 194 mol / l ) on day 6 .
laboratory tests at the age of 14 days showed that the plasma renin activity was 22.3 ng / ml / h [ 6 ng / l / s , normal , < 15 ng / ml / h ( < 4 ng / l / s ) ] , serum ace < 5 u / l ( normal , 8.321.4 u / l ) , plasma angiotensin i 2114 pg / ml [ 2114 ng / l , normal , < 180 pg / ml ( < 180 ng / l ) ] , plasma angiotensin ii 61 pg / ml [ 61 ng / l , normal , < 50 pg / ml ( < 50 ng
/ l ) ] and serum aldosterone 371 pg / ml [ 371 ng / l , normal , 5194 pg / ml ( 5194 ng / l ) ] . mutational analysis of the ace gene revealed novel compound heterozygous mutations , c.g776a [ p.arg(cgc)259his(gag ) ] inherited from the mother and c.1454delc [ p.pro(cct)485leu(ctt)fs ] inherited from the mother . at the age of 1 month , oral fludrocortisone treatment ( 0.1 mg / day ) was started to correct intermittent hyponatremia and hypokalemia .
the baby was discharged at the age of 4 months with a serum creatinine level of 0.6 mg / dl ( 53 umol / l ) .
the patient is currently 2 years old with normal blood pressure and serum electrolyte levels and mild impairment of renal function [ serum creatinine 0.5 mg / dl ( 44 mol / l ) and estimated glomerular filtration rate 69 ml / min/1.73 m ( 1.15 ml / s/1.73 m ) ] .
his weight and height are below the third percentile for his age , but his motor and cognitive functions are normal .
to date , five cases surviving the neonatal period of ar - rtd have been reported [ 58 ] .
all of the patients except patient 3 had one or more affected siblings , all of which died during the perinatal period .
although all of the patients subsequently developed chronic kidney disease , their psychomotor and cognitive development was normal .
case reports of ar - rtd patients surviving the neonatal perioda 
  ckd , chronic kidney disease ; tpl , kidney transplantation ; pd , peritoneal dialysis ; tx , treatment .
the patient 's elder sibling had been born at 33 weeks gestation and died of respiratory impairment just 15 h after birth . however , no autopsy was performed .
spontaneous ileal perforation could have resulted from low perfusion pressure , and another case of rtd with multiple ileal perforation has previously been described .
hypocalvaria is also the consequence of low blood pressure because skull membranous bones require high oxygen tension for normal growth [ 4 , 10 ] .
renal hypoperfusion is probably the cardinal lesion leading to ar - rtd because the same tubular lesions can be produced secondarily by various fetal conditions associated with insufficient renal blood supply and consequent marked stimulation of the ras , including renal artery stenosis and fetal exposure to ras blockers .
therefore , the presumed consequence of all mutations observed in ar - rtd is the absence of angiotensin ii production or function .
however , the profiles of ras components vary according to the underlying genetic defect of individual patient . a patient with
ace mutations revealed a high plasma renin activity , high active renin concentration and low ace concentration , as shown in the present case .
in addition , the present case revealed markedly increased angiotensin i level with mildly increased angiotensin ii and aldosterone levels .
the interpretation of the hormonal changes in the present case may be as follows : ( i ) production of angiotensin i , the substrate of ace , is markedly increased to overcome the defective ace activity , ( ii ) the missense ( p.r259h ) mutant ace has minimal residual function or other proteolytic enzyme systems are activated due to defective ace function and ( iii ) a small portion of markedly increased angiotensin i is converted to angiotensin ii by minimally functioning mutant ace or via other proteolytic enzyme systems ( figure 1 ) .
the compensatory increase of angiotensin ii may be the cause of survival and milder course of the patient .
schreiber et al .   recommended an early trial of mineralocorticoids to overcome extreme hypotension and hyperkalemia in patients with rtd .
possible sequential changes in the renin  angiotensin  aldosterone system in the present case .   decreased or absent ace activity due to genetic mutations ,   compensatory overproduction of angiotensin i , the substrate of ace and   conversion of a small portion of angiotensin i to angiotensin ii by minimally functioning mutant ( p.r259h ) ace or via other proteolytic enzyme systems such as chymases and tissue plasminogen activators ( t - pa ) . in conclusion , ar - rtd is not a uniformly fatal disease , although all of the surviving cases subsequently developed chronic kidney disease . collection of more surviving cases is required to find out possible prognostic factors and to develop effective treatment .
 autosomal - recessive renal tubular dysgenesis ( ar - rtd ) is a rare disorder caused by a genetic defect in the renin  
 angiotensin system . 
 although ar - rtd has typically been known as a lethal disease due to refractory hypotension and renal failure immediately after birth , few cases have reported survival of the neonatal period . 
 we report here an additional case of ar - rtd , who had novel ace mutations and survived over 2 years and provide a review of the five previously reported surviving cases . in conclusion , 
 ar - rtd is not a uniformly fatal disease , although factors affecting the survival remain unknown . 
Background
Case report
Discussion