Suggested guidelines for the diagnosis and management of urea cycle disorders.

Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with hyperammonemia either shortly after birth (~50%) or, later at any age, leading to death or to severe neurological handicap in many survivors. Despite the existence of effective therapy with alternative pathway therapy and liver transplantation, outcomes remain poor. This may be related to underrecognition and delayed diagnosis due to the nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity. These guidelines aim at providing a trans-European consensus to: guide practitioners, set standards of care and help awareness campaigns. To achieve these goals, the guidelines were developed using a Delphi methodology, by having professionals on UCDs across seven European countries to gather all the existing evidence, score it according to the SIGN evidence level system and draw a series of statements supported by an associated level of evidence. The guidelines were revised by external specialist consultants, unrelated authorities in the field of UCDs and practicing pediatricians in training. Although the evidence degree did hardly ever exceed level C (evidence from non-analytical studies like case reports and series), it was sufficient to guide practice on both acute and chronic presentations, address diagnosis, management, monitoring, outcomes, and psychosocial and ethical issues. Also, it identified knowledge voids that must be filled by future research. We believe these guidelines will help to: harmonise practice, set common standards and spread good practices with a positive impact on the outcomes of UCD patients.

Metabolic syndrome in childhood.

The so-called epidemic of childhood obesity has increased the interest in the metabolic syndrome (MS) due to the potential projection into adulthood. Prevalence of the MS in adolescents has been estimated to be 6.7% in young adults and 4.2% in adolescents. Figures rise up to 28.7% in overweight and obese adolescents. The most widely accepted hypothesis links the syndrome to obesity. In the Bogalusa study, the best predictors were obesity and being in the upper quartile of basal insulin levels. Ethnic and genetic factors play a role in order to explain the syndrome in the non-obese population and the differences of interobesity. The relationship between MS and type 2 diabetes and cardiovascular disease is well established in adults. This association can be suggested in children as well, although the syndrome in childhood urgently needs to be clearly defined. In this age group, it is also of great interest to identify diagnosis criteria of the so-called pre-MS. Detection of the syndrome focuses mainly on obese and overweight young people. Other population groups such as newborns with low or high birth weight, infants with accelerated growth, or children of obese or with gestational diabetes mothers are at a higher risk of developing peripheral insulin resistance. The measurement of abdominal circumference can be a useful screening tool. Physical exercise and restriction of saturated and trans fatty acids are basic for treatment. If reducing weight is necessary, a reduction of carbohydrate intake, especially for refined sugars, must be emphasised. Dietary fibre improves insulin sensitivity.

Long-chain polyunsaturated fatty acids in rat maternal milk, offspring brain and peripheral tissues in essential fatty acid deficiency.

Fatty acid status in humans is usually related to plasma or red blood cell fatty acid profiles. The aim of the study was to explore whether a maternal deficiency in dietary essential fatty acids would differentially affect lipid fractions in several tissues of the offspring, including brain. Female Wistar rats were fed an essential fatty acid-deficient diet during 3 months before mating. The fatty acid composition of different lipid fractions was examined in maternal milk, and in plasma, red blood cells, liver, adipose tissue, cerebral cortex and hippocampus of the offspring using thin layer and capillary column gas chromatography. Lipid fractions from most tissues of deprived offspring showed a common fatty acid profile characterized by elevated 20:3 omega9/20:4 omega6 ratio, and decreased docosahexaenoic acid and arachidonic acid. However, arachidonic acid was not affected in brain, even though 22:5 omega6 was increased in phospholipids of cerebral cortex and hippocampus. The present results demonstrate different degrees of resistance to essential fatty acid deficiency in lipid fractions and tissues. This suggests a priority distribution of arachidonic acid to preferential areas and shows that blood phospholipid fatty acids do not exactly reflect brain phospholipid status.