Familial neonatal pulmonary haemorrhage associated with defects of the urea cycle

Abstract

Four families are reported in which nine neonatal deaths occurred out of thirteen pregnancies. Pulmonary haemorrhage was found at necropsy in all nine patients. In three families citrullinaemia was responsible and in one the diagnosis was found to be arginino succinic aciduria. The diagnoses were made on the basis of hepatic enzyme assay, together with urinary and plasma amino-acid analysis. The dead infants were born near or at term and all were in excess of 2.6 kg (range 2.6-3.8 kg). The unusual finding of multiple deaths occurring in mature infants within a family should alert the neonatologist to the possibility of an inborn error of metabolism involving the urea cycle. The deaths typically occurred during the first five days of life in infants considered healthy at birth and who became hypothermic subsequently and developed diffuse neurological signs. As the pattern of deaths is particularly distressing to the parents, early investigation of suspicious cases may avoid repetition in subsequent pregnancies. Biochemical and necropsy data will be presented together with speculation as to the causes of the pulmonary haemorrhage which were not due to a generalised coagulopathy.