Prenatal diagnosis and treatment for fetal angiotensin converting enzyme deficiency

Abstract

Objective: To elucidate an etiology in a case with persistent oligohydramnios by prenatal diagnosis and actively treat the case to achieve good prognosis.

Methods: We performed whole exome sequencing (WES) of DNA from the fetus and parents. Serial amnioinfusions were conducted until birth. Pressors were required to maintain normal blood pressure. The infant angiotensin-converting enzyme (ACE) activity, angiotensin II (Ang II, a downstream product of ACE), and compensatory enzymes (CEs) activities were measured. Compensatory enzyme activities in plasma from age-matched healthy controls were also detected.

Results: We identified a fetus with a severe ACE mutation prenatally. The infant was born prematurely without pulmonary dysplasia. Hypotension and anuria resolved spontaneously. He had almost no ACE activity, but his Ang II level and CE activity exceeded the upper limit of the normal range and the upper limit of the 95% confidence interval of controls, respectively. His renal function also largely recovered.

Conclusion: Fetuses with ACE mutations can be diagnosed prenatally through WES. Serial amnioinfusion permits the continuation of pregnancy in fetal ACE deficiency. Compensatory enzymes for defective ACE appeared postnatally. Renal function may be spared by preterm delivery; furthermore, for postnatal vasopressor therapy to begin, improving renal perfusion pressure before nephrogenesis has been completed.

FIGURE 1

Clinical assessment of the infant. Panel A shows the infant’s mean blood pressure (MBP) curve from birth to the time of blood pressure (BP) stabilization. The two solid lines represent the MBP fluctuation range of the infant, and the dotted lines represent the normal range. Arrows indicated that there are changes in the types or doses of medication. The red asterisk represents medication stop time. DA, Dopamine; DOBU, Dobutamine; NE, Norepinephrine. The medication units are μg/kg/min. Panel B shows the infants growth and development. The red, blue and green lines represent length, head circumference and weight, respectively. Panel C-H shows the infants urine output, sodium (Na⁺), potassium (K⁺), renal function and renal tubular function, respectively. In Panel G, the red and blue lines represent alpha 1-microglobulin and retinol binding protein (RBP), respectively. In Panel H, the red and blue lines represent N-acetyl-β-D-glucosidase (NAG) and beta 2-microglobulin, respectively. Panel I shows the infants Ang II level. The range between dotted lines represents the normal range, whereas the solid lines represent the infant.