Diagnosis and management of glutaric aciduria type I – revised recommendations

Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline

Improved N-retention during L-carnitine-supplemented total parenteral nutrition

The influence of intravenously administered L-carnitine on lipid- and nitrogen-metabolism was studied during total parenteral nutrition of piglets (mean weight 4077 g; n = 9). The infusion protocol was divided into three isocaloric and isonitrogenous 48-hr periods. Amino acids (3 g/kg day) were administered throughout all three periods: 140 cal/kg/day were given as nonprotein calories, consisting only of glucose during period 1; during periods 2 and 3, an amount of glucose calorically equivalent to 4 g fat/kg/day was substituted with a lipid emulsion, and L-carnitine (1.5 mg/kg/day) was added in period 3. Key parameters of fat- and nitrogen-metabolism were determined during the entire regime. Indirect calorimetry was performed and the respiratory quotient calculated during all three periods. The results demonstrate a more effective lipolysis and oxidation of fatty acids during L-carnitine supplementation. These changes produce an increased energy gain from exogenously administered fat and a distinct improvement in nitrogen balance

Waardering van de baten van milieubeleid in Nederland

This study seeks to set priorities for environmental policy in the Netherlands. We focused on seven environmental issues including: climate change, acidification, low level ozone, particulate matter, noise, eutrophication and land contamination. These issues are prioritised using three different approaches: damage assessment, public opinion and 'disability adjusted life years'(DALYs). According to the damage assessment approach the priorities, in terms of potential benefits from full control, are low level ozone, land contamination and particulate matter, followed by acidification and climate change, whilst noise and eutrophication are estimated to yield the lowest potential benefits from control. However, in the absence of cost estimates no conclusions can be reached on the desirability of control measures. Public opinion surveys show that environmental issues other than the seven considered in this study are a major concern for the Dutch public, namely chemical release and oil pollution. However, focusing on the seven issues considered in this study, the Dutch public rank, climate change, acidification, eutrophication and air pollution from cars (interpreted as low-level ozone and PM10) as the issues of most concern. According to the DALYs approach the health effects of air pollution from particulate matter, and to a certain degree from low level ozone, dominate the disease burden. The future disease burden is largely due to changes in the population structure, i.e. an increasing, aged population. Another environmental problem associated with a high disease burden is noise exposure from road and air traffic. Based on a simple 'Borda count', a final ranking for the environmental issues is made. This study concludes that land contamination, climate change and particulate matter are top priority environmental issues in the Netherlands, followed by acidification, low level ozone, eutrophication and finally noise. These findings suggest that future policies focusing on the top issues may yield considerable benefit depending on their cost of control. Although ranking environmental issues is useful in the sense of highlighting priority issues and indicating if there is any surprise environmental issues for the Netherlands. It is important to note that the benefit estimates offer only some guidance on environmental priorities, in the absence of data on costs of implementing policies only part of the picture necessary for establishing priorities is provided. For a full-scale economic analysis benefit estimates need to be compared with cost estimates within a CBA framework. This is outside the scope of this study, however a separate paper on the issues relating to and experience with such CBAs is presented in Annex II

Waardering van de baten van milieubeleid in Nederland

Abstract niet beschikbaarThis study seeks to set priorities for environmental policy in the Netherlands. We focused on seven environmental issues including: climate change, acidification, low level ozone, particulate matter, noise, eutrophication and land contamination. These issues are prioritised using three different approaches: damage assessment, public opinion and 'disability adjusted life years'(DALYs). According to the damage assessment approach the priorities, in terms of potential benefits from full control, are low level ozone, land contamination and particulate matter, followed by acidification and climate change, whilst noise and eutrophication are estimated to yield the lowest potential benefits from control. However, in the absence of cost estimates no conclusions can be reached on the desirability of control measures. Public opinion surveys show that environmental issues other than the seven considered in this study are a major concern for the Dutch public, namely chemical release and oil pollution. However, focusing on the seven issues considered in this study, the Dutch public rank, climate change, acidification, eutrophication and air pollution from cars (interpreted as low-level ozone and PM10) as the issues of most concern. According to the DALYs approach the health effects of air pollution from particulate matter, and to a certain degree from low level ozone, dominate the disease burden. The future disease burden is largely due to changes in the population structure, i.e. an increasing, aged population. Another environmental problem associated with a high disease burden is noise exposure from road and air traffic. Based on a simple 'Borda count', a final ranking for the environmental issues is made. This study concludes that land contamination, climate change and particulate matter are top priority environmental issues in the Netherlands, followed by acidification, low level ozone, eutrophication and finally noise. These findings suggest that future policies focusing on the top issues may yield considerable benefit depending on their cost of control. Although ranking environmental issues is useful in the sense of highlighting priority issues and indicating if there is any surprise environmental issues for the Netherlands. It is important to note that the benefit estimates offer only some guidance on environmental priorities, in the absence of data on costs of implementing policies only part of the picture necessary for establishing priorities is provided. For a full-scale economic analysis benefit estimates need to be compared with cost estimates within a CBA framework. This is outside the scope of this study, however a separate paper on the issues relating to and experience with such CBAs is presented in Annex II.Ministerie van Economische Zake