Nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD): An evidence- and consensus-based approach.

The nutrition management guideline for very-long chain acyl-CoA dehydrogenase deficiency (VLCAD) is the fourth in a series of web-based guidelines focusing on the diet treatment for inherited metabolic disorders and follows previous publication of guidelines for maple syrup urine disease (2014), phenylketonuria (2016) and propionic acidemia (2019). The purpose of this guideline is to establish harmonization in the treatment and monitoring of individuals with VLCAD of all ages in order to improve clinical outcomes. Six research questions were identified to support guideline development on: nutrition recommendations for the healthy individual, illness management, supplementation, monitoring, physical activity and management during pregnancy. This report describes the methodology used in its development including review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; expert input through two Delphi surveys and a nominal group process; and external review from metabolic physicians and dietitians. It includes the summary statements of the nutrition management recommendations for each research question, followed by a standardized rating based on the strength of the evidence. Online, open access of the full published guideline allows utilization by health care providers, researchers and collaborators who advise, advocate and care for individuals with VLCAD and their families and can be accessed from the Genetic Metabolic Dietitians International (https://GMDI.org) and Southeast Regional Genetics Network (https://southeastgenetics.org/ngp) websites.

A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: A pilot study.

Low blood docosahexaenoic acid (DHA) is reported in patients with phenylketonuria (PKU); however, the functional implications in adolescents and adults are unknown. This pilot study investigated the effect of supplemental DHA on cognitive performance in 33 females with PKU ages 12-47 years. Participants were randomly assigned to receive DHA (10mg/kg/day) or placebo for 4.5 months. Performance on cognitive processing speed and executive functioning tasks was evaluated at baseline and follow up. Intention-to-treat and per protocol analyses were performed. At follow up, biomarkers of DHA status were significantly higher in the DHA-supplemented group. Performance on the cognitive tasks and reported treatment-related adverse events did not differ. While no evidence of cognitive effect was seen, a larger sample size is needed to be conclusive, which may not be feasible in this population. Supplementation was a safe and effective way to increase biomarkers of DHA status (www.clinicaltrials.gov; Identifier: NCT00892554).

Experimental evaluation of antidepressant effect of Vacha (Acorus calamus) in animal models of depression.

Depression is a common diagnosis throughout India. It is one of the major sequelae of modern lifestyle which is full of stress. Several drugs and therapies have been tried but a safe and effective treatment of depressive illness is yet not fully established. The main objective of this experimental study on animal models is to evaluate the antidepressant action of plant drug Vacha (Acorus calamus). The behavioral study was conducted and at the same time 5-HT receptor involvement was evaluated. The experimental study was done in rats to evaluate their Open Field Behavior (OFB), High Plus Maze (HPM) activity and 5-hydroxytryptamine (5-HT) receptor syndrome, before and after feeding Vacha. Concurrent Vacha administration in the depression model prevented the development of behavioral deficit in ambulation and rearing due to stress. Similarly, in High Plus Maze Test (HPMT), exploratory activity of rat was restored with Vacha administration. In adopted model of depression, when the animal was subjected to Vacha administration, the behavioural deficit was prevented very well as compared to stressed group. While eliciting the 5-HT syndrome, only two components out of five were influenced by Vacha, indicating that Vacha does not sensitize postsynaptic 5-HT1A receptors, which explains the behavioral deficit prevention in stressed rat group. Vacha definitely has antidepressant effects in animal model of depression.

Chlamydia trachomatis infection during pregnancy and the risk of preterm birth: a case-control study.

Our goal was to define the risks of preterm birth associated with Chlamydia trachomatis (CT) and other sexually transmitted infections (STIs) among pregnant women. We accessed clinical records from July 2005 to February 2008. The study population included all pregnant women who gave birth to a singleton newborn of at least 20 weeks' gestation, and who had antenatal care information. We estimated the impact of CT and other STI on the odds of preterm birth using logistic regression. Overall, 2127 women were included in this analysis. The prevalence of CT infection was 4.7%. CT diagnosis was not associated with preterm birth. In conclusion, this study did not find an association between CT and preterm birth. The lack of an association may be explained by early treatment. Future studies evaluating the timing of screening for STIs may help clarify whether pregnant women would benefit more from earlier screening.

Nutritional management of patients with urea cycle disorders.

The nutritional management of patients with urea cycle disorders (UCDs) involves restriction of dietary protein along with provision of adequate protein-free energy, essential amino acid supplements, and vitamins and minerals in combination with nitrogen-scavenging drugs. The present paper discusses nutrition therapy for a range of circumstances: during an acute hyperammonaemic episode and at hospital discharge; before, during, and after surgery; and for lifelong chronic management of UCDs.

A clinical study on cortisol and certain metabolites in some chronic psychosomatic disorders.

Present clinical study involved two groups of psychosomatic disorders, bronchial asthma and rheumatoid arthritis. In the study, the levels of plasma cortisol, blood glucose, total cholesterol and triglycerides were estimated in 125 clinical subjects, (50 normal controls, and 40 having bronchial asthma and 35 suffering from rheumatoid arthritis. The results showed a significant change in the levels of plasma cortisol and blood glucose in both the stressed clinical groups' vis-à-vis normal controls. The levels of atherogenic lipids (total cholesterol and triglycerides) were found quite elevated in both the diseased groups. However, in rheumatoid arthritis, the physiological changes were relatively more pronounced. The findings of this study indicate that rheumatoid arthritis is a relatively more chronic and late onset disorder as the functional performance of hypothalamopituitary-adrenocortical axis gradually declines with passage of time and the ability of the adrenocortical response to return to normalcy becomes impaired.

Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype.

Cystathionine beta-synthase (CBS) deficiency is a rare autosomal recessive disorder that is the most frequent cause of clinical homocystinuria. Patients not treated in infancy have multi-systems disorders including dislocated lenses, mental deficiency, osteoporosis, premature arteriosclerosis, and thrombosis. In this paper, we examine the relationship of the clinical and biochemical phenotypes with the genotypes of 12 CBS deficient patients from 11 families from the state of Georgia, USA. By DNA sequencing of all of the coding exons we identified mutations in the CBS genes in 21 of the 22 possible mutant alleles. Ten different missense mutations were identified and one novel splice-site mutation was found. Five of the missense mutations were previously described (G307S, I278T, V320A, T353M, and L101P), while five were novel (A226T, N228S, A231L, D376N, Q526K). Each missense mutation was tested for function by expression in S. cerevisiae and all were found to cause decreased growth rate and to have significantly decreased levels of CBS enzyme activity. The I278T and T353M mutations accounted for 45% of the mutant alleles in this patient cohort. The T353M mutation, found exclusively in four African American patients, was associated with a B(6)-nonresponsive phenotype and detection by newborn screening for hypermethioninemia. The I278T mutation was found exclusively in Caucasian patients and was associated with a B(6)-responsive phenotype. We conclude that these two mutations occurred after ethnic socialization and that the CBS genotype is predictive of phenotype.

Correlation of serotonin and monoamine oxidase levels with anxiety level in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is generally considered to have a psychogenic component in its physiopathology. AIM: To study the role of serotonin (5-hydroxytryptamine; 5-HT), monoamine oxidase (MAO) and anxiety, and to elucidate the relationship between these in patients with diarrhea-predominant IBS. METHODS: 5-HT and MAO activity and anxiety levels were studied in 20 healthy volunteers (aged 18-25 years; all men) and 57 patients with diarrhea-predominant IBS (30-60 years; all men). RESULTS: The concentrations of 5-HT (0.3 [0.04] microg/ mL) and MAO (15.5 [3.2] U/mL), and the anxiety level score (14.4 [2.9]) were significantly higher (p < 0.001) in patients than in healthy volunteers (0.1 [0.02], 6.4 [1.4] and 3.4 [1.2], respectively). These parameters correlated with each other in both patients and volunteers. CONCLUSIONS: Elevated 5-HT and MAO activity and anxiety may play a role in patients with diarrhea-predominant IBS.

Risk factors for premature ovarian failure in females with galactosemia.

UNLABELLED: The risk for premature ovarian failure (POF) in females with galactosemia can be predicted by analyzing 3 areas of risk pathology: the patient's molecular genotype for galactose-1-phosphate uridyltransferase (GALT), alternate pathways for galactose metabolism, and the patient's environment at diagnosis and during treatment. STUDY DESIGN: Retrospective cross-sectional information was collected on 53 females with classic galactosemia, and their ovarian function was analyzed by determination of serum follicle-stimulating hormone and luteinizing hormone levels and by clinical observation. The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2). RESULTS: The most prevalent mutation, Q188R, had a significant effect of genotype category (Q188R/Q188R, Q188R/Other, Other/Other) on POF (P =.04, Fisher exact test and an odds ratio of 8.3). Mean erythrocyte Gal-1-P level during treatment was a significant risk factor for POF (P =.04). Also, all patients studied with less than 5% total body oxidation of galactose to (13)CO(2) had POF, whereas those with more than 5% did not have POF (P =.008, Fisher exact test). CONCLUSION: The development of POF in females with galactosemia is more likely if the patient's genotype is Q188R/Q188R, if the mean erythrocyte Gal-1-P is >3.5 mg/dL during therapy, and if the recovery of (13)CO(2) from whole-body (13)C-galactose oxidation is reduced below 5% of administered (13)C-galactose.

Galactose breath testing distinguishes variant and severe galactose-1-phosphate uridyltransferase genotypes.

A galactose breath test that quantitates [1-(13)C]galactose conversion to 13CO2 provides information on the whole body galactose oxidative capacity. As there is little information on the relationship between whole body oxidation and the genotype in patients with galactosemia, we measured the 13CO2 excretion for 2 h after administration of [1-(13)C]galactose in 37 patients (3-48 y old) with galactose-1-phosphate uridyltransferase (GALT) deficiency and 20 control subjects (3-37 y old). Eleven patients with the common Q188R/Q188R genotype and no detectable erythrocyte GALT activity eliminated <2% of a bolus of [1-(13)C]galactose as 13CO2 compared with 8.47 to 28.23% in controls. This defines a severe metabolic phenotype. Seven patients with one Q188R allele and a second mutant allele such as L195P, E308K, V151A, M142K, or Q344K and one patient with a K285N/unknown genotype also released <2% as 13CO2 in 2 h. The presence of N314D or S135L as the second mutant allele does not impair total body galactose oxidation, as individuals with the GALT genotype of Q188R/N314D, K285N/N314D, and Q188R/S135L had normal 2-h galactose breath tests. Subjects with S135L/S135L, N314D/N314D, S135L/deltaT2359 as well as other rarer genotypes such as R258C/Y209C, E203K/IVSC-N314D, K285N/T138M, Q188R/D113N, S135L/F171S, R148W/N314D, and IVSC-N314D/N314D oxidized galactose comparable to controls. The dissociation of residual erythrocyte GALT activity and whole body galactose oxidative capacity is exemplified by blacks with a S135L/S135L genotype and absent erythrocyte GALT activity. An oral 2-h [1-(13)C]galactose breath test distinguishes severe and variant GALT genotypes and enables delineation of the extent of impaired galactose metabolism in an array of patients who possess diverse GALT mutations. It may prove to be useful in establishing whether a patient is capable of manifesting disease similar to patients with a Q188R/Q188R genotype.

Impact of a camp experience on phenylalanine levels, knowledge, attitudes, and health beliefs relevant to nutrition management of phenylketonuria in adolescent girls.

OBJECTIVE: To evaluate the effectiveness of an education intervention in a summer camp setting on knowledge, attitudes, and health beliefs regarding metabolic control of phenylketonuria and dietary compliance. DESIGN: An observational study of a weeklong metabolic camp for adolescent girls with phenylketonuria (PKU) who were followed up over the course of 1 year. Observations also were made in 3 subsequent years of camp. INTERVENTION: The camp experience consisted of diet and disease education, sessions on reproductive development, and recreation. Group discussions on attitudes and perceptions about PKU related to dietary compliance were held with nutritionists and a pediatric psychologist. OUTCOME MEASURES: Biochemical and psychological data were collected on the first and last days of the camp to assess short-term effects of the intervention, then at quarterly intervals during the year to determine the long-term impact of the camp. Precamp and Postcamp plasma amino acid data for the subsequent 3 years were also collected. SUBJECTS/SETTING: Analyses were based on 13 adolescent girls with PKU in the first year of a camp at Emory University in Atlanta, Ga, and compared with data from 11 additional campers enrolled the second year, 8 in the third year, and 7 in the fourth year. Mean age +/- standard deviation of first-year campers was 13 +/- 2 years, mean IQ +/- standard deviation was 98 +/- 16, and 9 of 13 girls had menstruated. STATISTICAL ANALYSES PERFORMED: Short-term effects of the intervention were computed by comparing mean levels of response from the baseline period to those from the last day of camp using t tests for dependent samples. Repeated-measures analysis of variance was used to assess the long-term effects of the camp experience over the course of a year at regular quarterly intervals. RESULTS: Short-term effects of the education intervention were significant reductions in dietary phenylalanine intake, plasma phenylalanine levels, and perceived isolation. However, these effects progressively returned to baseline levels over the course of a year. The significant short- and long-term effects of increased knowledge of diet and disease persisted throughout the study period. APPLICATIONS/CONCLUSIONS: Short-term effects of the education intervention resulted in improved metabolic control associated with improved attitudes, increased knowledge of diet and disease, increased perceived support, and decreased barriers to dietary compliance in a camp setting.

Outcomes analysis of verbal dyspraxia in classic galactosemia.

PURPOSE: This study evaluates a genotype/phenotype relationship between developmental verbal dyspraxia (DVD) and the common, missense mutation of the galactose-1-phosphate uridyltransferase gene, Q188R, in patients with classic galactosemia (G/G). METHODS: As part of this study, we devised a questionnaire for "speech problems" to be completed by the patient\'s clinician. To validate the questionnaire and determine its accuracy in detecting DVD, we analyzed questionnaire responses for 21 patients by testing them independently and directly for DVD through a speech pathologist blinded to the patients' genotype. RESULTS: We found that the questionnaire had a sensitivity of 0.56 and a specificity of 0.75. We then calculated the prevalence of DVD for a larger set of 113 patients with G/G galactosemia whose biochemical phenotype, molecular genotypes, and clinical status were known. The prevalence of "speech problems" from raw data were 50 of 113 (44.2%). After adjusting for misclassification, 43 (38.1%) were classified as cases of DVD. Using multivariate, logistic, regression analyses we found a significant interaction between genotype and mean red blood cell (RBC) galactose-1-phosphate (Gal-1-P). When corrected, using mean RBC Gal-1-P < h 3.28 mg%, the Q188R/Q188R genotype was the best predictor of DVD. There was a significant risk (odds ratio = 9.6, p = 0.0504) of having DVD associated with homozygosity for Q188R compared with other genotypes. CONCLUSIONS: We conclude that homozygosity for Q188R mutations in the GALT gene is a significant risk factor for DVD. However, poor metabolic control obviates this relationship as indicated by RBC Gal-1-P greater than 3.28 mg%.

Possible Correlates of Free Radicals and Free Radical Mediated Disorders in Ayurveda with Special Referance to Bhutagni Vyapara and Ama at molecular Level.

The description of metabolic processes, operating at various levels insider the body, has been essentially covered in Ayurveda under thirteen types of Agnis and their functions at different levels, which are often compared with the enzymes and biochemical which take part in biological and / or biophysical transformations and reactions. When these Agnis, at different levels, get disordered they lead to the production of certain undesired elements or byproducts in the system, which are called as 'Ama' in ayurveda and are considered as very important morbid factor responsible for causation of a variety of diseases and playing key role in genesis of most of the diseases.The present article attempts to correlate the most recent concept of today's medicine i.e., Free Radical concept with that of the concept of Agni and Ama, described in Ayurveda and thereby opens newer vistas of search for remedies from Ayurvedic research, which may be helpful in the prevention and care of Free Radical Mediated Diseases.

Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency.

PURPOSE: Primary carnitine deficiency is an autosomal recessive disorder caused by defective carnitine transport and manifests as nonketotic hypoglycemia or skeletal or heart myopathy. METHODS: To define the mechanisms producing partially reduced plasma carnitine levels in the parents of affected patients, we examined carnitine transport in vivo and in the fibroblasts of a new patient and his heterozygous parents. RESULTS: Kinetic analysis of carnitine transport in fibroblasts revealed an absence of saturable carnitine transport in the proband's cells and a partially impaired carnitine transport in fibroblasts from both parents, whose cells retained normal Km values toward carnitine (6-9 microM) but reduced Vmax. At steady state, normal fibroblasts accumulated carnitine to a concentration that was up to 80 times the extracellular value (0.5 microM). By contrast, cells from the proband had minimal carnitine accumulation, and cells from both parents had intermediate values of carnitine accumulation. Plasma carnitine levels were slightly below normal in both heterozygous, yet clinically normal, parents and in the paternal grandfather and the maternal grandmother. To define the mechanism producing partially decreased carnitine levels, we studied urinary carnitine losses in heterozygous parents compared with controls. Urinary losses increased linearly (P < 0.05) with plasma carnitine levels in normal controls. When urinary carnitine losses were normalized to plasma carnitine levels, a significant difference was observed between controls and heterozygous individuals (P < 0.01). CONCLUSIONS: These results indicate that fibroblasts from heterozygotes for primary carnitine deficiency have a decreased capacity to accumulate carnitine and that heterozygotes have increased urinary losses, which may contribute to their reduced plasma carnitine levels.

Alterations in the sensitivity of 5(th) receptor subtypes following chronic asvagandha treatment in rats.

Asvagandha (Withania somnifera) is an important antistress drug has now been sown to have an antidepressant action in clinically depressive patients, However, the mechanism of its antidepressant action has not been studied. Normal rats fed with asvagandha root extract (100mg/kg orally) for 4 and 8 weeks showed enhanced open field behavior and emotional stability along with a moderate but significant enhancement in the functional sensitivity of 5 HT2 receptors in the brain and a reciprocal subsensitivity of the 5HT1A receptors chronic asvagandha treatment (propylactically) was effective in preventing the behavioral deficit in open field activity in an animal model of depression. This was accompanied by an adaptive supersensitivity of the postsynaptic 5HT2 receptors in the brain. The effect of chronic Asvagandha on 5HT receptor subtypes is similar to the action of chronic ECT treatment and several antidepressant drugs.