Neonatal hyperammonaemia with complete absence of liver carbamyl phosphate synthetase activity.

Abstract

SUMMARY Two newborn infants, male (A) and female (B), with lethal hyperammonaemia are described in the same family. In both, symptoms started on the second day of life. Lethargy and hypotonia were the most prominent initial findings and were followed by convulsions and coma. In both, blood ammonia levels rose to 570 ,umol/l (798 ,ug/100 ml) a few hours before death, which occurred on the third and fourth day of life respectively. Assay of liver urea cycle enzymes in baby B showed a complete absence of mitochondrial carbamyl phosphate synthetase activity. cousins. Baby A was the product of the third pregnancy of the mother. The first had resulted in a miscarriage during the fourth month of pregnancy. The second baby was a term male who died 12 hours after birth without definite diagnosis, but with symptoms similar to those of babies A and B.Baby A appeared well at birth. Glucose-water feedings were started and he remained well until the end of the first 24-hour period when he became progressively lethargic, hypotonic, and refused feeds. During the second day his condition deteriorated, with tachypnoea, abdominal distension, and generalised tonic-clonic convulsions. He was transferred to the neonatal unit of this hospital at 40 hours.On admission he was comatose with frequent episodes of generalised convulsions. The primitive reflexes were lacking. The fontanelle was normal. Palpation of the liver and spleen was difficult because of the abdominal distension. Intravenous glucose 10 % was started and diazepam and phenobarbitone were given for the convulsions. A few hours after admission episodes of apnoea started and intubation with artificial ventilation was required. In spite of protein restriction and supportive measures, the baby died at 56 hours. During the last few hours of life, he expelled a characteristic odour of ammonia during respiration.Laboratory data included a normal blood count, blood glucose, and serum electrolytes, and calcium.Spinal tap was normal and blood and CSF cultures negative. Chest x-ray was normal, and aspartate and alanine transaminases (SGOT and SGPT) were 230 on 9 May 2018 by guest. Protected by copyright.

Carbamyl phosphate synthetase deficiency with lethal neonatal outcome

“…To our knowledge only thirteen families with isolated mitochondrial CPS deficiency have been documented (Hommes et al 1969;Arashima and Matsuda 1972;Odidvre et al 1973;Gelehrter and Snodgrass 1974;Batshaw et al 1975;Sheffield et al 1976;Farriaux et al 1977;Lambotte et al 1977;Mantagos et al 1978;Van Gennip et al 1980;Kline et al 1981;Reynolds et al 1981; this patient). In seven of them (Gelehrter and Snodgrass 1974;Sheffield et al 1976;Farriaux et al 1977;Lambotte et al 1977;Mantagos et al 1978;Van Gennip et al 1980; this patient) there was a rapidly fatal neonatal outcome i.e.…”

“…Plasma amino acids show an elevation of alanine, arginase. N-acetylglutamate is an obligate activator of carbamyl phosphate synthetase glutamine, glycine, lysine and, less frequently of c~-aminobutyric acid, glutamic acid and proline, while arginine and citrulline are decreased at least in the patients with a severe enzymatic deficiency (Farriaux et al 1977;Lambotte et al 1977;Mantagos et al 1978; this patient). This pattern is not pathognomonic, but is also found in ornithine transcarbamylase deficiency or even organic acidurias with hyperammonaemia.…”

“…In seven of them (Gelehrter and Snodgrass 1974;Sheffield et al 1976;Farriaux et al 1977;Lambotte et al 1977;Mantagos et al 1978;Van Gennip et al 1980; this patient) there was a rapidly fatal neonatal outcome i.e. death within ten days (Table I).…”

Interstitial deletion of chromosome 2q32‐34 associated with multiple congenital anomalies and a urea cycle defect (CPS I deficiency)

“…In addition to hyperammonemia, biochemical studies reveal a respiratory alkalosis, hyperglutaminemia, decreased or absent plasma citrulline, and absence of orotate in the urine [Brusilow and Maestri, 1996]. Autopsy findings have included Alzheimers Type II lesions in the brain [Brusilow and Maestri, 1996], hepatic microvesicular steatosis [Badizadegan and Perez-Atayde, 1997], and pulmonary hemorrhage [Sheffield et al, 1976;Mantagos et al, 1978].…”

“…It was initially described in 1969, by Kirkman and Kiesel, [1969] and subsequently by Freeman et al [1970]. The disorder manifests most often in the newborn period with vomiting followed by acute decompensation associated with hyperammonemic encephalopathy progressing to seizures and/or coma [Mantagos et al, 1978;Brusilow and Maestri, 1996]. In addition to hyperammonemia, biochemical studies reveal a respiratory alkalosis, hyperglutaminemia, decreased or absent plasma citrulline, and absence of orotate in the urine [Brusilow and Maestri, 1996].…”