N-acetylglutamate synthase deficiency with associated 3-methylglutaconic aciduria: A case report.

N-acetylglutamate synthase (NAGS) deficiency is a rare autosomal recessive disorder, which results in the inability to activate the key urea cycle enzyme, carbamoylphosphate synthetase 1 (CPS1). Patients often suffer life-threatening episodes of hyperammonaemia, both in the neonatal period and also at subsequent times of catabolic stress. Because NAGS generates the cofactor for CPS1, these two disorders are difficult to distinguish biochemically. However, there have now been numerous case reports of 3-methylglutaconic aciduria (3-MGA), a marker seen in mitochondrial disorders, occurring in CPS1 deficiency. Previously, this had not been reported in NAGS deficiency. We report a four-day-old neonate who was noted to have 3-MGA at the time of significant hyperammonaemia and lactic acidosis. Low plasma citrulline and borderline orotic aciduria were additional findings that suggested a proximal urea cycle disorder. Subsequent molecular testing identified bi-allelic pathogenic variants in NAGS. The 3-MGA was present at the time of persistent lactic acidosis, but improved with normalization of serum lactate, suggesting that it may reflect secondary mitochondrial dysfunction. NAGS deficiency should therefore also be considered in patients with hyperammonaemia and 3-MGA. Studies in larger numbers of patients are required to determine whether it could be a biomarker for severe decompensations.

Simple Nutrition Screening Tool for Pediatric Inpatients.

BACKGROUND: Pediatric nutrition risk screening tools are not routinely implemented throughout many hospitals, despite prevalence studies demonstrating malnutrition is common in hospitalized children. Existing tools lack the simplicity of those used to assess nutrition risk in the adult population. This study reports the accuracy of a new, quick, and simple pediatric nutrition screening tool (PNST) designed to be used for pediatric inpatients. MATERIALS AND METHODS: The pediatric Subjective Global Nutrition Assessment (SGNA) and anthropometric measures were used to develop and assess the validity of 4 simple nutrition screening questions comprising the PNST. Participants were pediatric inpatients in 2 tertiary pediatric hospitals and 1 regional hospital. RESULTS: Two affirmative answers to the PNST questions were found to maximize the specificity and sensitivity to the pediatric SGNA and body mass index (BMI) z scores for malnutrition in 295 patients. The PNST identified 37.6% of patients as being at nutrition risk, whereas the pediatric SGNA identified 34.2%. The sensitivity and specificity of the PNST compared with the pediatric SGNA were 77.8% and 82.1%, respectively. The sensitivity of the PNST at detecting patients with a BMI z score of less than -2 was 89.3%, and the specificity was 66.2%. Both the PNST and pediatric SGNA were relatively poor at detecting patients who were stunted or overweight, with the sensitivity and specificity being less than 69%. CONCLUSION: The PNST provides a sensitive, valid, and simpler alternative to existing pediatric nutrition screening tools such as Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), Screening Tool Risk on Nutritional status and Growth (STRONGkids), and Paediatric Yorkhill Malnutrition Score (PYMS) to ensure the early detection of hospitalized children at nutrition risk.

Sulphate in pregnancy.

Sulphate is an obligate nutrient for healthy growth and development. Sulphate conjugation (sulphonation) of proteoglycans maintains the structure and function of tissues. Sulphonation also regulates the bioactivity of steroids, thyroid hormone, bile acids, catecholamines and cholecystokinin, and detoxifies certain xenobiotics and pharmacological drugs. In adults and children, sulphate is obtained from the diet and from the intracellular metabolism of sulphur-containing amino acids. Dietary sulphate intake can vary greatly and is dependent on the type of food consumed and source of drinking water. Once ingested, sulphate is absorbed into circulation where its level is maintained at approximately 300 µmol/L, making sulphate the fourth most abundant anion in plasma. In pregnant women, circulating sulphate concentrations increase by twofold with levels peaking in late gestation. This increased sulphataemia, which is mediated by up-regulation of sulphate reabsorption in the maternal kidneys, provides a reservoir of sulphate to meet the gestational needs of the developing foetus. The foetus has negligible capacity to generate sulphate and thereby, is completely reliant on sulphate supply from the maternal circulation. Maternal hyposulphataemia leads to foetal sulphate deficiency and late gestational foetal death in mice. In humans, reduced sulphonation capacity has been linked to skeletal dysplasias, ranging from the mildest form, multiple epiphyseal dysplasia, to achondrogenesis Type IB, which results in severe skeletal underdevelopment and death in utero or shortly after birth. Despite being essential for numerous cellular and metabolic functions, the nutrient sulphate is largely unappreciated in clinical settings. This article will review the physiological roles and regulation of sulphate during pregnancy, with a particular focus on animal models of disturbed sulphate homeostasis and links to human pathophysiology.