The advisory report 'Neonatal screening' from the Health Council of The Netherlands

The Health Council of the Netherlands has published an advisory report on neonatal screening in view of developments in diagnostics, therapy and the prevalence of neonatal diseases. Currently it involves screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia. Because screening may lead to considerably better outcomes in affected newborns, the council recommends expanding current screening to include medium-chain acyl-CoA dehydrogenase deficiency, sickle-cell disease and 12 other rare disorders: biotinidase deficiency, galactosaemia, glutaricaciduria type I, HMG-CoA lyase deficiency, holocarboxylase-synthetase deficiency, homocystinuria, isovaleric-acidaemia, long-chain hydroxyacyl-CoA dehydrogenase deficiency, maple syrup urine disease, 3-methylcrotonyl-CoA carboxylase deficiency, tyrosinaemia I and very-long-chain acyl-CoA dehydrogenase deficiency. A better detection method for cystic fibrosis must be developed before it is included in screening to restrict the number of sweat-test referrals of unaffected newborns. The council recommends providing information on neonatal screening during pregnancy and gives special attention to the possibility of detecting carriership in the parents.     

遗传代谢病枫糖尿症研究进展

枫糖尿症(MSUD)是由于支链氨基酸及其衍生的α-酮异已酸、α-酮异戊酸等在血和脑脊液中蓄积,间接地抑制α-羟酸的分解,致使α-羟丁酸和α-羟异戊酸在患儿的尿和汗液中大量排泄,形成特异焦糖味而被称之为“枫糖尿症”。如果MSUD不能及时治疗将导致癫痫发作、昏迷、甚至死亡。本文对MSUD的发病机制,临床诊断及治疗研究进展进行综述。     

一例夫妻均为枫糖尿病基因携带者的多次妊娠结局报道及文献复习

枫糖尿病是一种临床罕见的遗传性疾病，其发病机制是由于基因异常表达导致人体支链α-酮酸脱氢酶复合体缺乏所致，多见于新生儿期或者婴儿期发病，大脑是主要受累器官，常表现为精神或者神经症状，严重者可致患儿死亡，临床治疗极为棘手，严重影响着女性生殖健康结局。本文通过报道1例临床极为罕见的夫妻双方均为枫糖尿病基因携带者的多次妊娠结局，并对枫糖尿病相关文献进行复习，总结该病的病因、发病机制、临床表现、诊断和治疗等特点，以期拓宽临床医生的视野，在今后的临床工作中对该病保持高度警觉，对可疑孕产妇尽早进行基因检测并进行科学指导，以保护女性生殖健康。     

The need of essential amino acids in children. An evaluation based on the intake of phenylalanine, tyrosine, leucine, isoleucine, and valine in children with phenylketonuria, tyrosine amino transferase defect, and maple syrup urine disease

The diet of children with blocks in the metabolism of five amino acids has been investigated to evaluate the need for these amino acids in the maintenance of normal growth and development. Two children with phenylketonuria, one child with tyrosine aminotransferase defect and one child with maple syrup urine disease are included in the study. The growth and development of the children have been within the normal range except for language development, which was retarded in the maple syrup urine disease child. The need for phenylalanine, phenylalanine and tyrosine combined and isoleucine, leucine, and valine for protein synthesis in growing children was investigated by registering the intake of phenylalanine in the phenylketonuria children, the intake of phenylalanine and tyrosine in the tyrosine amino transferase defect child and isoleucine, leucine and valine in the maple syrup urine disease child. The significance of this intake, defined as the sufficient intake, is discussed, as well as the difference between the sufficient intake and requirement. The sufficient intake is compared with former studies on requirement. There is good agreement between the sufficient intake and requirement of phenylalanine and tyrosine. The sufficient intake of isoleucine, leucine, and valine as judged from our study is lower than in former studies on requirement.     

Selenium responsive myositis during prolonged home total parenteral nutrition in cystic fibrosis

The need for routine supplementation of total parenteral nutrition solutions with selenium (Se) has not been clearly defined. Although clinical selenium deficiency in patients on prolonged total parenteral nutrition has been reported, it is rarely observed in the United States. We report a 19-year-old woman with cystic fibrosis who developed muscle pain and weakness after 3 months on total parenteral nutrition which was not supplemented with Se. Coincident with her onset of symptoms, markedly elevated serum creatine kinase values were observed compared to baseline levels. Subsequent evaluations revealed undetectable (less than 0.02 microgram/ml) serum and urine Se levels in this patient. In addition, electromyographic evidence of myositis and nonspecific membrane irritability was documented. Therapy with oral Se rapidly reversed her symptoms and normalized with serum creatine kinase values over a 10-day period. Prolonged treatment with Se was required to achieve normal values of Se in the serum. Patients with severe pancreatic insufficiency, such as cystic fibrosis, may be at risk for clinical Se deficiency if on prolonged total parenteral nutrition without supplementation. Elevated creatine kinase levels should alert physicians to the possibility of Se deficiency in such patients.     

Nutrient intakes of adolescents with phenylketonuria and infants and children with maple syrup urine disease on semisynthetic diets.

Adequacy of nutrient intakes of adolescents with and without phenylketonuria (PKU) and infants and children with and without maple syrup urine disease (MSUD) were assessed using 3-day diet records sorted by disease and by age of the subject. Mean intakes of all nutrients were greater than two-thirds of the Recommended Dietary Allowances (RDA) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDI) for all adolescents studied, with the exception of selenium (Se) in PKU adolescents, which averaged 27.8 micrograms. For adolescents with PKU, > 50% of the RDA or ESADDI for all nutrients was provided by elemental or modified protein hydrolysate medical foods, except for vitamin A in children aged 11-15 years and Se in children 11-18 years. Mean nutrient intakes of all infants and children were greater than two-thirds of the RDA or ESADDI for all nutrients except Se in MSUD children aged 1-11 years, where intakes ranged from 6.4 to 13.2 micrograms (21-66% of the RDA). The medical foods provided for most of the RDA and ESADDI recommendations, with the exception of Se in MSUD children.     

Comparative analysis of maple syrups and natural sweeteners: Carbohydrates composition and classification (differentiation) by HPAEC-PAD and FTIR spectroscopy-chemometrics

Maple syrup is a natural sweetener obtained from the sap of maple trees (Acer saccharum), highly rich in bioactive molecules placing it among the most desirable and natural sweeteners for human consumption (agave, sugarcane, corn and honey). Carbohydrate profiles (amounts and composition) as well as FTIR-PCA classification of maple syrup were performed and compared to other natural sweeteners. TLC and HPAEC-PAD revealed that maple syrup exhibits unique carbohydrate profiles dominated by high sucrose content (511–688 mg/g) followed by glucose and fructose traces. Alternately and highly relevant, it was possible to identify three oligosaccharides, not previously reported in maple syrup, with potential to be used as authenticity markers. The FTIR spectra displayed the most characteristic differences in the carbohydrate region (1185–950 cm⁻¹), particularly, maple syrup exhibited strong absorption bands at 997 and 1054 cm⁻¹ wavelengths in agreement with their high sucrose content. Principal component analysis of the FTIR carbohydrates region allowed maple syrup to be distinguished from other natural sweeteners based on botanical source. The above information would be helpful for the authentication, characterization, and subsequent detection of intentional adulteration of this natural sweetener.     

Assistance nutritionnelle dans la mucoviscidose pourquoi ? quels résultats ?

The prognosis in cystic fibrosis is related to nutritional status. While new enzyme preparations can be used to prepare suitable diets for these patients, the natural history of the disease and the progressive malnutrition may require nutritional support. This is essentially provided as nocturnal enteral feeding and occasionally by the parenteral route. Improvements are obtained not only in terms of anthropometric patterns but also in terms of ventilatory function. Nutritional support may be also extremely useful when preparing patients for transplantation.     

Selecting technologies for assessment

This article describes criteria used by several organizations to select technologies for assessment and the factors that are common to most lists of criteria. It presents a framework or model (called TAPSS) that relates the most important factors. The model can be used to estimate the expected impact of an assessment on health and economic outcomes for a population. It incorporates information on such factors as the health and economic importance of the disease addressed by the technology, the expected impact of the technology on health and economic outcomes, variations in the technology's current use, and factors affecting the production and reception of an assessment. The article includes an example of an application of the method--screening for maple syrup urine disease.     

Characteristics of Resting Metabolic Rate in Critically Ill,Mechanically Ventilated Adults With Cystic Fibrosis

Background: Critically ill patients with cystic fibrosis may be especially sensitive to the negative consequences of overfeeding and underfeeding, yet there is almost no information available about the energy needs of these patients. The purpose of this study was to characterize the metabolic rate of critically ill adult patients with cystic fibrosis requiring mechanical ventilation. Methods: This was an observational study in which the resting metabolic rate, oxygen consumption, and carbon dioxide production of adult patients with cystic fibrosis requiring critical care, sedation, and mechanical ventilation were measured with indirect calorimetry. This group was compared with a cohort of adult critical care patients without cystic fibrosis. Results: Twelve patients with cystic fibrosis were identified and measured. These were compared with a control group of 25 critically ill patients. Both groups were underweight (body mass index, 17.4 ± 4.0 kg/m² in cystic fibrosis and 18.4 ± 2.3 kg/m² in control). Adjusting for differences in age, sex, height, and weight, there was no difference in resting metabolic rate between the cystic fibrosis and control groups (1702 ± 193 vs 1642 ± 194 kcal/d, P = .388). Measured resting metabolic rate matched predicted values 58% of the time in cystic fibrosis and 60% of the time in control. Conclusions: The resting metabolic rate of sedated adult patients with cystic fibrosis being assisted with mechanical ventilation is not different from that of adult critical care patients without cystic fibrosis. In both these underweight groups, accurate prediction of resting metabolic rate is difficult to obtain.     

A maple syrup extract alleviates liver injury in type 2 diabetic model mice

A recent study showed that 54% of type 2 diabetes (T2D) patients have nonalcoholic fatty liver disease, which is a risk factor for aggravation diabetic symptoms. Previous studies suggested components in maple syrup alleviated liver injury and found polyphenols as food components to improve the symptoms and complications of diabetes. Therefore, we hypothesized that a polyphenol fraction in maple syrup improves the symptoms and complications of diabetes. To address the hypothesis, we investigated the effects of a polyphenol-rich maple syrup extract (MSE) on a T2D model mice. KK-A^y mice were fed a normal or 0.1% MSE-supplemented diet for 43 days. The results showed that the levels of serum alanine aminotransferase and aspartate aminotransferase were significantly reduced in mice that ingested MSE. Hepatic genes related to lipogenesis and lipolysis were down- and upregulated, respectively, in mice that ingested MSE. These results suggest that MSE intake alleviates liver injury and suppresses lipid accumulation in the livers of T2D mice.     

Lowered concentrations of branched-chain amino acids result in impaired growth and neurological problems: insights from a branched-chain alpha-keto acid dehydrogenase complex kinase-deficient mouse model

Excess circulating levels of branched-chain amino acids (BCAA), as seen in maple syrup urine disease, result in severe neuropathology. A new mouse model, deficient in the kinase that controls BCAA catabolism, shows that very low circulating levels of BCAA are also associated with neuropathology, including the development of epileptic seizures. These mice clearly demonstrate the need to control essential amino acid levels within both upper and lower limits.     

A comparative physicochemical analysis of maple (Acer saccharum Marsh.) syrup produced in North America with special emphasis on seasonal changes in Nova Scotia maple syrup composition

Maple syrup is produced by concentrating the maple tree sap. The physicochemical profile of maple syrup can be varied depending on the processing method, microbial contamination, seasonal and geographical variations etc. Apart from being a better alternative to refined sugar, the minerals and phenolics in maple syrup may provide additional health benefits owing to their bioactivities. We studied the physicochemical profiles of maple syrup samples from North America and the seasonal compositional changes of the syrup from Nova Scotia (NS). Syrup pH, color, Brix were significantly differ depending on the location. Brix values ranged from 61.6 to 70.2°. Thirteen different phenolics including protocatechuic acid, coniferyl alcohol, vanillin, and syringic aldehyde were identified and quantified. The total mineral content ranged from 2.6 to 4.8 g/L of syrup. Potassium was the most abundant, followed by calcium, magnesium, phosphorus, manganese, and zinc. Analyses of NS syrup during early, mid and late seasons revealed that, total phenolics and minerals increased and the syrup color became darker towards late season. Syrup pH, brix and sugars did not differ among the seasons. Interestingly, vanillin, syringic acid and syringic aldehyde were the main phenolics in early maple syrup samples while protecatechuic acid was the predominant in late season.     

Challenges in the dietary treatment of cystic fibrosis related diabetes mellitus

Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.     

Zinc nutriture and taste acuity in patients with cystic fibrosis

An assessment of zinc nutriture was undertaken in 19 juvenile patients with cystic fibrosis and 40 control adolescents. Plasma zinc concentration, hair zinc content and quantitative taste acuity score were determined in each individual. In the patients, these data were related to other clinical data. No difference in plasma zinc between patients and controls was found. Moreover, no correlation between biochemical indices of zinc status and growth attainment was seen in contradistinction to a previously reported suggestion that growth-retarded patients were more prone to zinc depletion. Hair zinc was significantly lower and taste acuity thresholds significantly higher in the patients with cystic fibrosis. The impairment in taste acuity contrasts with an earlier report on taste in patients with this disease. Hair zinc levels declined as forced vital capacity of the lungs decreased as a consequence of the pulmonary disease. From the evidence presented in this investigation and in previously reported studies, zinc metabolism appears to be altered in cystic fibrosis; it is likely that impaired zinc nutriture occurs more commonly in patients afflicted with cystic fibrosis than in the population at-large.     

2010年西安地区高危婴幼儿中遗传代谢病筛查情况分析

【目的】 总结2010年来西安地区高危婴幼儿中先天性遗传代谢性疾病的发病情况和治疗经验,以期提高临床医疗工作者对先天性遗传代谢性疾病的重视程度、认识和处理能力。 【方法】 对2010年1-12月在西安地区共33家医院就诊的高危婴幼儿104例,应用高效液相串联质谱技术的方法进行35种遗传代谢性疾病的筛检。 【结果】 104例高危儿,7例确诊为先天性遗传代谢病,阳性率为6.7%。病种依次为:甲基丙二酸血症3例,一过性酪氨酸血症1例,同型胱氨酸尿症1例,枫糖尿病1例,中链酰基辅酶A脱氢酶缺乏症1例。 【结论】 西安地区先天性遗传代谢性疾病在有高危因素的婴幼儿人群中发生率极高,按发生率高低排序依次为有机酸代谢病、氨基酸酸代谢病及脂质代谢病。早期的筛查不仅对患儿及家庭早期干预有利,也有利于医院确诊病因,减少医疗纠纷的发生,值得进一步推广开展。     

Is there a case for n-3 fatty acid supplementation in cystic fibrosis?

PURPOSE OF REVIEW: This review evaluates our current knowledge on the association of fatty acid abnormalities in cystic fibrosis with the disease process, and makes a case for a well-designed clinical trial to evaluate the clinical efficacy of long chain n-3 fatty acids. RECENT FINDINGS: It has long been known that cystic fibrosis patients exhibit fatty acid abnormalities, but these have not been well investigated in tissues affected by the disease. Recent studies have demonstrated that such tissues do indeed show abnormalities in the proportions of linoleic, arachidonic and docosahexaenoic acids, and have demonstrated alterations in fatty acid and phospholipid metabolism in cystic fibrosis. Work in other areas has identified novel anti-inflammatory actions of long chain n-3 fatty acids that might be relevant to cystic fibrosis. A recent systematic review of fish oil supplementation in cystic fibrosis did not allow firm conclusions to be drawn, but suggested that there may be some benefits. SUMMARY: The restoration of abnormal fatty acid profiles may be beneficial in cystic fibrosis, but this approach has not been evaluated in studies with a suitable design to permit firm conclusions to be drawn. There is a need for a long-term randomized controlled study to evaluate the therapeutic benefit of fish oil supplementation in cystic fibrosis.     

Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats

We showed elevated plasma levels of branched-chain amino acids, alpha-ketoacids, alpha-hydroxyacids in thiamin-deprived rats, which had decreased liver thiamin levels (2.4% of control) after 4 weeks of feeding of thiamin-deficient diet. The ratios of mean levels of these acids in thiamin-deficient rats to those in control rats were as follows: total branched-chain amino acids 1.6; total branched-chain alpha-ketoacids 2.7; total branched-chain alpha-hydroxyacids 3.6; pyruvic acid 1.6. The plasma level of total branched-chain alpha-hydroxyacids was correlated to liver thiamin concentration (r = -0.67, p less than 0.01), but those of the other two acids were not correlated. Although the increased levels of branched-chain acids in thiamin-deprived rats were less remarkable than those of ill patients with maple syrup urine disease, they reflect the reportedly decreased branched-chain alpha-ketoacid dehydrogenase activities (about 40% of control), and we discussed whether the toxic effects of individual branched-chain acid could be demonstrated by its administration to the thiamin-deprived rats.     

Low dietary zinc alters indices of copper function and status in postmenopausal women

OBJECTIVES: To better define the relationship between dietary zinc and copper for humans so that sound recommendations for intakes of these elements can be made. METHODS: A study was conducted to ascertain the effect of moderately excessive and deficient intakes of zinc on copper metabolism and use in humans fed low and luxuriant amounts of copper. Twenty-one postmenopausal women housed in a metabolic unit completed the study as designed. After a 10-d equilibration period in which they were fed a diet providing 31.5 micromol (2 mg) Cu and 91.8 micromol (9 mg) Zn/8.4 MJ (2000 kcal), the women were divided into two groups. One group was fed a diet containing 15.7 micromol (1 mg) Cu/8.4 MJ (2000 kcal), and the other group was fed a diet containing 47.2 micromol (3 mg) Cu/8.4 MJ (2000 kcal). After equilibration, both groups were fed the basal diet providing 45.9 micromol (3 mg) Zn/8.4 MJ (2000 kcal) for 90 d; this was followed by another 10-d equilibration period before dietary zinc was increased to 811 micromol (53 mg)/8.4 MJ (2000 kcal) for 90 d. RESULTS: The women were in positive copper balance only when the diet provided 47.2 micromol (3 mg) Cu and 811 micromol (53 mg) Zn/d. Immunoreactive ceruloplasmin concentrations and platelet cytochrome-c oxidase activity on a platelet number basis were significantly lower and the ratio between enzymatic and immunoreactive ceruloplasmin was significantly higher during low dietary than during high dietary zinc intake. Serum cholesterol was higher in subjects fed 15.7 micromol (1 mg) Cu/d than in those fed 47.2 micromol (3 mg) Cu/d. Total and low-density lipoprotein cholesterol concentrations decreased with zinc supplementation. Whole-blood glutathione concentration and erythrocyte glutathione peroxidase activity were lower during high than during low dietary zinc intake. CONCLUSIONS: The findings indicate that an inadequate intake of zinc (45.9 micromol/d; 3 mg/d) was more effective than a moderately high intake of zinc (811 micromol/d; 53 mg/d) in inducing changes associated with a decreased copper status in postmenopausal women. Furthermore, the findings indicate that copper status indicators might be useful in evaluating changes in zinc status in humans, and an intake of 15.7 micromol (1 mg)/d of copper may be inadequate for postmenopausal women.     

Compliance of the diet restricted with leucine, isoleucine and valine in maple syrup urine disease (MSUD) children

The aim of this study was to evaluate the compliance of the diet with limited branched-chain amino acids (BCAA) content in long-term observation of patients with maple syrup urine disease (MSUD). The study group consisted of 7 children at age of 1.5-18 years. Nutrition evaluation was based on current diet records from 3-4 days, every 3-4 months. Energy and nutrition values of proposed daily products lists and diet records was compared with adequate references and recommendations. Energy and content of most of the nutrients in proposed daily products lists were in agreement with RDI except calcium. Diet analysis at MSUD children revealed insufficient contents of: iron, zinc, copper, vitamin B1, B2, niacin and vitamin C (often below 90% RDI).