Transient Hyperammonemia of the Preterm Infant

Ballard, Roberta A.; Vinocur, Barry; Reynolds, John W.; Wennberg, Richard P.; Merritt, Allen; Sweetman, Lawrence; Nyhan, William L.

doi:10.1056/nejm197810262991704

Cited by 105 publications

(40 citation statements)

References 26 publications

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“…Inborn errors of metabolism, including urea cycle defects and many of the organic acidemias, are at the top of the list. Also in the differential diagnosis in the neonate is a condition referred to as transient hyperammonemia of the newborn (THAN), 3 whereas in the older infant, fatty acid oxidation defects may be considered. Ammonia levels in newborns with these conditions frequently exceed 1000 mol/L.…”

Section: Hyperammonemiamentioning

confidence: 99%

Inborn Errors of Metabolism in Infancy: A Guide to Diagnosis

1998

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ABSTRACT. Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis for many of these conditions. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in this review. Indications for specific laboratory studies are discussed. Guidelines are provided for the stabilization and emergency treatment of critically ill infants. This approach will identify those infants who will benefit from additional evaluation and specific treatment.Many of the inborn errors of metabolism, including urea cycle defects, organic acidemias, and certain disorders of amino acid metabolism, present in the young infant with symptoms of an acute or chronic metabolic encephalopathy. Typical symptoms include lethargy, poor feeding, apnea or tachypnea, and recurrent vomiting. Metabolic acidosis and/or hyperammonemia are observed in many of these conditions, but there are notable exceptions, including nonketotic hyperglycinemia and molybdenum co-factor deficiency. Therefore, appropriate laboratory testing for metabolic disorders should be performed in any infant who exhibits these findings. Although sepsis may be the initial consideration in a neonate with these symptoms, inborn errors of metabolism should always be in the differential diagnosis, particularly in a full-term infant with no specific risk factors.Hypoglycemia may be the predominant finding in a number of inborn errors of metabolism, including glycogen storage disorders, defects in gluconeogenesis, and fatty acid oxidation defects. The latter disorders, among the most common encountered, exhibit marked clinical variability and also may present as a sudden death, a Reye's-like episode, or a cardiomyopathy. Jaundice or other evidence of hepatic dysfunction is the mode of presentation of another important group of inborn errors of metabolism including galactosemia, hereditary tyrosinemia, neonatal hemochromatosis, and a number of other conditions. A subset of lysosomal storage disorders may present very early with coarse facial features, organomegaly, or even hydrops fetalis. Specific patterns of dysmorphic features and congenital anomalies characterize yet another group of inherited metabolic disorders, such as Zellweger syndrome and the Smith-Lemli-Opitz syndrome. Each of these symptom complexes, and the appropriate evaluation of the affected infants, is discussed in more detail in this review. Pediatrics 1998; 102(6). URL: http://www.pediatrics.org/cgi/content/full/ 102/6/e69; inborn errors of metabolism, inherited metabolic disorders.ABBREVIATIONS. CNS, central nervous system; THAN, transient hyperammonemia of the newborn; OTC, ornithine transcarbamylase; CoA, co-enzyme A; PDH, pyruvate dehydrogenase; GSD, glycogen storage disease. T he number, complexity, and varied clinical presentation of inborn errors of metabolism present a formidable chal...

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Section: Hyperammonemiamentioning

confidence: 99%

Inborn Errors of Metabolism in Infancy: A Guide to Diagnosis

1998

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“…Ammonia is toxic to the central nervous system and has been implicated in the pathogenesis of several neurological conditions, including hepatic encephalopathy (Hazell and Butterworth, 1999), inborn errors of the urea cycle (Brusilow and Horwich, 1994;Brusilow and Maestri, 1996), Reye's syndrome (Pranzatelli and De Vivo, 1987), organic acidurias (Bachmann and Colombo, 1980), valproate toxicity (Coulter and Allen, 1981;Batshaw and Brusilow, 1982), transient hyperammonemia in infants (Ballard et al, 1978), and idiopathic hyperammonemia (Watson et al, 1985;Frere et al, 2000). The mechanism of ammonia neurotoxicity remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Glutamine‐induced free radical production in cultured astrocytes

Jayakumar

Rao

Schousboe

et al. 2004

Glia

109

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Ammonia is a neurotoxin implicated in the pathogenesis of hepatic encephalopathy, Reye's syndrome, inborn errors of the urea cycle, glutaric aciduria, and other metabolic encephalopathies. Brain ammonia is predominantly metabolized to glutamine in astrocytes by glutamine synthetase. While the synthesis of glutamine has generally been viewed as the principal means of ammonia detoxification, this presumed beneficial effect has been questioned as growing evidence suggest that some of the deleterious effects of ammonia may be mediated by glutamine rather than ammonia per se. Since ammonia is known to induce the production of free radicals in cultured astrocytes, we investigated whether such production might be mediated by glutamine. Treatment of astrocytes with glutamine (4.5 mM) increased free radical production at 2-3 min (95%; P < 0.05), as well as at 1 and 3 h (42% and 49%, respectively; P < 0.05). Similarly treated cultured neurons failed to generate free radicals. Free radical production by glutamine was blocked by the antioxidants deferoxamine (40 microM) and alpha-phenyl-N-tert-butyl-nitrone (250 microM), as well as by the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (500 microM). Free radical production was also blocked by 6-diazo-5-oxo-L-norleucine (1 mM), an inhibitor of glutaminase, suggesting that ammonia released by glutamine hydrolysis may be responsible for the generation of free radicals. Additionally, the mitochondrial permeability transition inhibitor, cyclosporin A, blocked free radical production by glutamine. The results indicate that astrocytes, but not neurons, generate free radicals following glutamine exposure. Glutamine-induced oxidative and/or nitrosative stress may represent a key mechanism in ammonia neurotoxicity.

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“…The right parieto-occipital lead was evaluated according to the method of Laidlaw (28). In selected 50-sec epochs, frequencies 5 12 Hz were counted, and a histogram was constructed. The percentage of the tracing contributed by each frequency was then calculated.…”

Section: Methodsmentioning

confidence: 99%