A Premature Infant With Renal Tubular Dysgenesis Who Survived 61 Days With Anuria

Abstract

Autosomal recessive renal tubular dysgenesis (AR-RTD) is a rare and typically lethal disorder of the renin-angiotensin system (RAS), caused by mutations in genes such as angiotensinogen (AGT), renin (REN), angiotensin-converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1). It is characterized by severe hypotension, anuria, and features of Potter sequence, usually resulting in fetal or neonatal death. Although more than 15 surviving cases have been reported, survival has generally been associated with non-truncating mutations. We report the case of a premature male infant born at 34 weeks' gestation with clinical features of AR-RTD and confirmed homozygosity for a novel truncating ACE variant (c.2691delC, p.Phe898SerfsTer14). The pregnancy was complicated by oligohydramnios and fetal growth restriction, and the infant showed no urinary output throughout his life. Despite a poor prognosis, he survived for 61 days with intensive multidisciplinary support but without renal replacement therapy. Initial management included mechanical ventilation, nitric oxide, vasopressin for refractory hypotension, and strict restriction of fluid and electrolyte intake. Lactulose was administered enterally from day 32 of life to mitigate uremic symptoms, potentially aiding in the excretion of nitrogenous waste via the immature intestinal mucosa. The patient ultimately succumbed to renal failure on day 61 of life. Genetic testing confirmed the diagnosis, but parental testing was not performed. A literature review identified 61 genetically confirmed ACE-related AR-RTD cases, with an overall survival rate of 24.6%. Survival was significantly lower among patients with biallelic truncating mutations (8.6%) compared to those with at least one non-truncating allele. While truncating mutations were generally associated with poorer outcomes, exceptions existed, and variant location within the gene did not consistently predict prognosis. Interestingly, more reported mutations clustered on the 3' end, although disease severity tended to be higher with 5' variants. This case is notable as the longest known survival of a patient with confirmed AR-RTD and complete anuria, without renal replacement. The relatively prolonged survival may be attributed to the early initiation of supportive therapy immediately after birth, even before genetic confirmation. Importantly, the time gained allowed for meaningful genetic counseling and family bonding. This report underscores that survival beyond the neonatal period may be possible in AR-RTD cases with truncating ACE variants when early diagnosis and multidisciplinary management are initiated. It highlights the importance of prompt clinical suspicion and supportive care in maximizing life expectancy and enabling family-centered care, even in cases expected to have a dismal prognosis.

Keywords: angiotensin-converting enzyme; anuria; autosomal recessive renal tubular dysgenesis; renal tubular dysgenesis; renin-angiotensin system.

Figure 1. The clinical management of the patient.

SIMV: synchronized intermittent mandatory ventilation, HFO: high-frequency oscillatory, iNO: nitric oxide inhalation therapy, RBC: red blood cell, MCT formula: medium chain triglycerides formula

Figure 2. The ultrasound image of the kidney on admission.

Both kidneys were highly echoic, with reduced corticomedullary differentiation.

Figure 3. Color Doppler ultrasound on admission.

The blood flow of both kidneys was normal.

Figure 4. ACE structure and the reported variants.

Truncating variants are shown over the gene, and non-truncating variants are shown under the gene. The present case is shown with an underline. ACE: angiotensin-converting enzyme