Severe hyponatremia in a neonate with Costello syndrome and CoA during PGE1 infusion.Our patient was born at 35 wk' gestation due to premature rupture of membranes.His birthweight was 3,698 g (100th centile) and occipitofrontal circumference 35.0 cm (98.9th centile).He presented with facial dysmorphism, slightly shortened limbs, and loose skin.Initial postnatal echocardiogram revealed coarctation of the aorta (CoA) and hypertrophic cardiomyopathy.PGE1 was started on the first day of life (DOL) to maintain the ductus arteriosus (DA) patency.The lipo-PGE1 infusion was temporarily terminated to determine the tolerance of DA closure on DOL2.However, as CoA became symptomatic following DA closing, PGE1-cyclodextrin (CD) infusion was initiated on DOL3.After the initiation of PGE1-CD, ductal patency was maintained.However, PGE1-CD was replaced by lipo-PGE1 because of the frequent apnea on DOL4.Unfortunately, the CoA gradually became symptomatic and, therefore, lipo-PGE1 was replaced by a high dosage of PGE1-CD (50-75 ng/kg/ min) again on DOL8.Intermittent injection of furosemide was also initiated on the same day because of congestive heart failure and chylothorax.A CHD is identified in 45% of patients with Costello syndrome; however, CoA is very rare and only one case has been reported.PGE1 infusion is widely used to maintain DA patency in neonates with critical CHDs.Fever, apnea, and periosteal thickening have been reported as adverse effects of PGE1 therapy.Fluid-electrolyte disturbances, especially hyponatremia, are also important adverse effects of this therapy; however, report of severe hyponatremia is rare.This case showed severe hyponatremia, even though sodium loading was initiated and the loading dose was increased.Excess urinary excretion of sodium was considered a major cause of hyponatremia.Increased urinary excretion of sodium led to hypovolemia, resulting in elevated plasma renin activity, aldosterone, and antidiuretic hormone levels.The adverse effects of PGE1 infusion are dose dependent.A relatively high dose of PGE1-CD is the most possible explanation for the severity of hyponatremia in this case, because PGE1 promotes sodium excretion by acting on the renal tubule.Another possible explanation for the severity of hyponatremia in this case is the HRAS mutation.In fact, hyponatremia due to of renal sodium wasting has been reported in neonates with RASopathies, including Costello syndrome.Thus, increased HRAS activity, identified in Costello syndrome, may contribute to the excess of urinary sodium excretion in this case.Addnl., injection of furosemide, along with PGE1-CD, increased the levels of brain natriuretic peptide resulting from heart failure.Preterm birth may also have enhanced renal sodium wasting and affected the severity of hyponatremia in this case.In conclusion, this case highlights that careful monitoring of serum electrolytes is required in neonates with RASopathies who are treated with a high dose of PGE1.
