Effect of Maternal Marginal Zinc Deficiency on Development, Redox Status, and Gene Expression Related to Oxidation and Apoptosis in an Avian Embryo Model.

Maternal severe zinc (Zn) deficiency resulted in growth retardation and high mortality during embryonic development in human. Therefore, this study is aimed at evaluating the effect of maternal marginal Zn deficiency on the development and redox status to avoid severe Zn deficiency using an avian model. A total of 324 laying duck breeders at 214 days old were randomly allotted into 3 dietary Zn levels with 6 replicates of 18 ducks per replicate. The birds were fed experimental diets including 3 dietary supplemental Zn levels of 0 mg/kg (maternal Zn-deficient group, 29.2 mg Zn/kg diet), 60 mg/kg (maternal Zn-adequate group), and 120 mg/kg (maternal Zn-high group) for 6 weeks. Dietary Zn levels had on effect on egg production and fertility (P > 0.05), whereas dietary Zn deficiency decreased breeder plasma Zn concentration and erythrocytic alkaline phosphatase activity at week 6 and inhibited erythrocytic 5'-nucleotidase (5'-NT) activity at weeks 2, 4, and 6 (P < 0.05), indicating that marginal Zn-deficient status occurred after Zn depletion. Maternal marginal Zn deficiency increased embryonic mortality and contents of superoxide anion radical, MDA, and PPC and reduced MT content and CuZnSOD activity in duck embryonic livers on E29. The MDA content was positively correlated with embryonic mortality. Maternal marginal Zn deficiency increased BCL2-associated X protein and Caspase-9 mRNA expressions as well as decreased B-cell lymphoma-2 and MT1 mRNA and signal AKT1 and ERK1 protein expressions (P < 0.05). Breeder plasma Zn concentration and erythrocytic 5'-NT activities at week 6 were positively correlated with GSH-Px activity and GPx, MT1, and BCL2 mRNA expressions in embryonic livers on E29. In conclusion, erythrocytic 5'-NT activity could be more rapid and reliable to monitor marginal Zn-deficient status. Marginal Zn deficiency impaired hatchability and antioxidant defense system and then induced oxidative damage and apoptosis in the embryonic liver, contributing to the greater loss of duck embryonic death.

Physiological responses and transcriptomic changes reveal the mechanisms underlying adaptation of Stylosanthes guianensis to phosphorus deficiency.

BACKGROUND: Phosphorus (P) is an essential macronutrient for plant growth that participates in a series of biological processes. Thus, P deficiency limits crop growth and yield. Although Stylosanthes guianensis (stylo) is an important tropical legume that displays adaptation to low phosphate (Pi) availability, its adaptive mechanisms remain largely unknown. RESULTS: In this study, differences in low-P stress tolerance were investigated using two stylo cultivars ('RY2' and 'RY5') that were grown in hydroponics. Results showed that cultivar RY2 was better adapted to Pi starvation than RY5, as reflected by lower values of relative decrease rates of growth parameters than RY5 at low-P stress, especially for the reduction of shoot and root dry weight. Furthermore, RY2 exhibited higher P acquisition efficiency than RY5 under the same P treatment, although P utilization efficiency was similar between the two cultivars. In addition, better root growth performance and higher leaf and root APase activities were observed with RY2 compared to RY5. Subsequent RNA-seq analysis revealed 8,348 genes that were differentially expressed under P deficient and sufficient conditions in RY2 roots, with many Pi starvation regulated genes associated with P metabolic process, protein modification process, transport and other metabolic processes. A group of differentially expressed genes (DEGs) involved in Pi uptake and Pi homeostasis were identified, such as genes encoding Pi transporter (PT), purple acid phosphatase (PAP), and multidrug and toxin extrusion (MATE). Furthermore, a variety of genes related to transcription factors and regulators involved in Pi signaling, including genes belonging to the PHOSPHATE STARVATION RESPONSE 1-like (PHR1), WRKY and the SYG1/PHO81/XPR1 (SPX) domain, were also regulated by P deficiency in stylo roots. CONCLUSIONS: This study reveals the possible mechanisms underlying the adaptation of stylo to P deficiency. The low-P tolerance in stylo is probably manifested through regulation of root growth, Pi acquisition and cellular Pi homeostasis as well as Pi signaling pathway. The identified genes involved in low-P tolerance can be potentially used to design the breeding strategy for developing P-efficient stylo cultivars to grow on acid soils in the tropics.

Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution.

BACKGROUND: Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD). METHODS: In this cohort study we included eight pediatric patients (six males), age 0.9-14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin. RESULTS: All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDS[Formula: see text]T0: -1.58 ± 0.92, IGF1/IGFBP3 molar ratio-SDS[Formula: see text]T0: -1.58 ± 0.88). At T12, IGF1-SDS increased significantly (∆T0-12: 1.63 ± 1.40, p = 0.01), and IGFBP3-SDS and IGF1/IGFBP3 molar ratio-SDS showed a trend toward an increase. In the three children within the childhood growth period (post-infancy, pre-puberty) height-SDS increased (∆height-SDST0-12: 0.57 ± 0.06, p = 0.003) despite substantial weight loss. CONCLUSIONS: These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth.

A Personalised Dietary Approach-A Way Forward to Manage Nutrient Deficiency, Effects of the Western Diet, and Food Intolerances in Inflammatory Bowel Disease.

This review discusses the personalised dietary approach with respect to inflammatory bowel disease (IBD). It identifies gene-nutrient interactions associated with the nutritional deficiencies that people with IBD commonly experience, and the role of the Western diet in influencing these. It also discusses food intolerances and how particular genotypes can affect these. It is well established that with respect to food there is no "one size fits all" diet for those with IBD. Gene-nutrient interactions may help explain this variability in response to food that is associated with IBD. Nutrigenomic research, which examines the effects of food and its constituents on gene expression, shows that-like a number of pharmaceutical products-food can have beneficial effects or have adverse (side) effects depending on a person's genotype. Pharmacogenetic research is identifying gene variants with adverse reactions to drugs, and this is modifying clinical practice and allowing individualised treatment. Nutrigenomic research could enable individualised treatment in persons with IBD and enable more accurate tailoring of food intake, to avoid exacerbating malnutrition and to counter some of the adverse effects of the Western diet. It may also help to establish the dietary pattern that is most protective against IBD.

Marginal iron deficiency enhances liver triglyceride accumulation in rats fed a high-sucrose diet.

We investigated whether marginal iron-deficiency (MID) without anemia influences liver lipid accumulation in rats. Ingestion of a MID diet in which the iron concentration was half of AIN-93 formulation (iron-adequate, IA) for 3 weeks decreased liver iron concentration without anemia. We then evaluated the influence of the MID diet on liver lipid accumulation in combination with a high-sucrose (HS) diet and confirmed that the HS-MID diet successfully decreased liver iron concentration without anemia. Additionally, a significant increase in liver triglyceride concentration was found, accompanied by upregulation of hepatic fatty acid synthase expression in the rats fed the HS-MID diet compared to those in the rats fed an HS-IA diet, although no difference was observed in plasma transaminase activity and hepatic interleukin-1ß expression. These results suggest that MID enhances de novo lipid synthesis via upregulation of lipogenic gene expression in combination with sucrose in the diet. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; HS, high sucrose; IA, iron adequate; ID, iron deficiency; MID, marginal irondeficiency; NAFLD, non-alcoholic fatty liver disease.

The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin.

The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt's syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown. Recent genomic approaches have revealed the physiological importance of zinc transporters in skin formation and clarified their functional impairment in cutaneous pathogenesis. In this review, we provide an overview of the relationships between zinc deficiency and skin disorders, focusing on the roles of zinc transporters in the skin. We also discuss therapeutic outlooks and advantages of controlling zinc levels via zinc transporters to prevent cutaneous disorganization.

The Evolving Role of Multivitamin/Multimineral Supplement Use among Adults in the Age of Personalized Nutrition.

Micronutrient deficiencies occur in segments of the adult population in the United States. Multivitamin/multimineral supplements (MVMS) are widely used by this population, which reduces inadequacies in micronutrient intake, but the potential for exceeding tolerable upper intake levels in others should be considered. There are concerns associated with the excessive intake of certain nutrients, particularly folic acid, and potential untoward consequences. The advent of nutrigenomics and the enhanced ability to directly study the interactions between nutrition and genetic variants and expression will allow for the conduct of more targeted studies with specific endpoints and may ultimately lead to progress in the field of personalized nutrition. The role of MVMS in health maintenance and chronic disease prevention remains controversial. Conducting studies in this area has been hampered by, among other factors, inconsistent definitions of MVMS, ranging from as few as three vitamins to broad-spectrum products containing more than two dozen vitamins and minerals. Results from some observational studies and large-scale, randomized, controlled trials suggest that MVMS may reduce the risk of some forms of cancer and, potentially, cardiovascular disease. The ongoing COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is expected to build on this research and provide additional insights into these areas.

Inherited Disorders of Manganese Metabolism.

While the neurotoxic effects of manganese were recognized in 1837, the first genetic disorder of manganese metabolism was described only in 2012 when homozygous mutations in SLC30A10 were reported to cause manganese-induced neurotoxicity. Two other genetic disorders of manganese metabolism have now been described - mutations in SLC39A14 cause manganese toxicity, while mutations in SLC39A8 cause manganese and zinc deficiency. Study of rare genetic disorders often provides unique insights into disease pathobiology, and the discoveries of these three inherited disorders of manganese metabolism are already transforming our understanding of manganese homeostasis, detoxification, and neurotoxicity. Here, we review the mechanisms by which mutations in SLC30A10, SLC39A14, and SLC39A8 impact manganese homeostasis to cause human disease.

Toll-like receptor 4 antagonist TAK-242 inhibits autoinflammatory symptoms in DITRA.

BACKGROUND: IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), and loss-of-function mutations in IL36RN define a recessively inherited autoinflammatory disease named "deficiency of IL-36Ra" (DITRA). DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy. OBJECTIVE: We aimed to elucidate the role of toll-like receptor 4 (TLR4) signaling in DITRA and to innovate an efficient treatment for DITRA. METHODS: We generated Il36rn-/- mice and treated them with TLR4 agonist to establish DITRA model mice. Furthermore, we administrated TLR4 antagonist TAK-242 to the model mice to inhibit the DITRA symptoms. RESULT: Il36rn-/- mice treated by TLR4 agonist showed autoinflammatory symptoms in skin, articulation and liver. Thus, we established model mice for DITRA or GPP that show cutaneous, articular, and hepatic autoinflammatory symptoms typical of DITRA or GPP: sterile pustules on the skin, liver abscesses and enthesitis of the hind paws. Additionally, these symptoms were canceled by TAK-242 administration. We demonstrated the inhibitory effects of the TLR4 antagonist TAK-242 on the autoinflammatory symptoms exhibited by the DITRA models. CONCLUSION: We suggested that blockage of TLR4 signaling is a promising treatment for DITRA and GPP.

A Specific Activity-Based Probe to Monitor Family GH59 Galactosylceramidase, the Enzyme Deficient in Krabbe Disease.

Galactosylceramidase (GALC) is the lysosomal ß-galactosidase responsible for the hydrolysis of galactosylceramide. Inherited deficiency in GALC causes Krabbe disease, a devastating neurological disorder characterized by accumulation of galactosylceramide and its deacylated counterpart, the toxic sphingoid base galactosylsphingosine (psychosine). We report the design and application of a fluorescently tagged activity-based probe (ABP) for the sensitive and specific labeling of active GALC molecules from various species. The probe consists of a ß-galactopyranose-configured cyclophellitol-epoxide core, conferring specificity for GALC, equipped with a BODIPY fluorophore at C6 that allows visualization of active enzyme in cells and tissues. Detection of residual GALC in patient fibroblasts holds great promise for laboratory diagnosis of Krabbe disease. We further describe a procedure for in situ imaging of active GALC in murine brain by intra-cerebroventricular infusion of the ABP. In conclusion, this GALC-specific ABP should find broad applications in diagnosis, drug development, and evaluation of therapy for Krabbe disease.

Dietary zinc deficiency impairs humoral and cellular immune responses to BCG and ESAT-6/CFP-10 vaccination in offspring and adult rats.

BACKGROUND: Besides being the world's most widely used vaccine, BCG is the most controversial vaccine in current use. Estimates of protection impaired by BCG against pulmonary TB vary from nil to 80%. Dietary zinc deficiency has been confirmed to impair the immune function of animals. However, knowledge about effects of mild dietary zinc deficiency and the time of vaccination on BCG vaccine responsiveness in offspring and adult rats is limited. This work investigated the consequences of feeding zinc deficient and normal zinc diets to rats during gestation, infancy or adulthood on the immune responses to BCG vaccination. METHODS: On gestation day 0, sixteen maternal rats were divided into two groups and fed with diets bellow: a control diet ad libitum (30 µg zinc/g diet, NC), a zinc deficient diet ad libitum (8 µg zinc/g diet, ZnD). Pup rats were served as experimental subjects. From day 1 of pregnancy upon delivery, maternal rats were given a standard diet (30 mg/kg/day zinc) or zinc deficient diet (8 mg/kg/day zinc) respectively. Adult male 10-week Wistar rats were divided into two dietary groups for 17 weeks of feeding: a control diet ad libitum (30 µg zinc/g diet, NC), a zinc deficient diet ad libitum (8 µg zinc/g diet, ZnD). The birth time of newborn pups was recorded as the zero week. For adult male rats, the time of receiving different assigned diet was recorded as the zeroth week. Newborn pups of these maternal rats were immunized with BCG vaccine or MTB antigen ESAT-6/CFP-10 at postnatal 0 and 2 week. The adult male rats were immunized on the 12th and 14th week. Then, blood samples, thymus and spleen from the rats were harvested for detection of humoral and cell-mediated immune responses using ELISA, MTT and QRT-PCR analysis. Decreased INF-γ and TNF-α production in plasma, changes of expression level of ZIP2, ZIP8, NF-κB and IL-6 mRNA in immune organs, together with reduced T cell proliferation was observed in pups and adult BCG rats suffered from dietary zinc deficiency. Small differences were observed between rats received BCG vaccine and MTB antigen ESAT-6/CFP-10. RESULTS: Our data clearly indicate that dietary zinc deficiency can weaken the plasma cytokine levels and cell-mediated responses to BCG and ESAT-6/CFP-10 vaccine via decreasing T cell proliferation, down-regulating INF-γ and TNF-α production and affecting the expression of ZIP2, ZIP8, NF-κB and IL-6 mRNA. In addition, the vaccine immunogenicity of BCG and ESAT-6/CFP-10 was not significantly affected by the time of vaccination.

The effect of the paraoxonase 1 (PON1) T(-107)C polymorphism on serum PON1 activity in women is dependent on fatty acid intake.

Paraoxonase 1 (PON1) is an enzyme that prevents the peroxidation of lipoprotein and cell membranes. Our hypothesis is that the effect of the PON1 T(-107)C polymorphism on serum PON1 activity in healthy adult women is dependent on their fatty acid intake profile. This study included women (n = 39) who completed a food frequency questionnaire. Fatty acid intake was estimated based on the interview and a nutrient reference table. Blood samples were collected for genotyping and to measure serum PON1 activity. Serum PON1 activity was different among genotypes and was higher for women of the CC genotype (P < .001). Women in the study were categorized in 2 groups according to the median nutrient intake. Overall, there was a difference (P < .05) in serum PON1 activity between the CC and TT genotypes in women ingesting either above or below the median total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, omega 3 (n-3) and omega 6 (n-6; P < .05). However, genotype effects on serum PON1 activity were not observed in women ingesting below the median (15:1) ratio of n-6/n-3 (P > .05) but were observed in women ingesting above the ratio of n-6/n-3 (P < .05). This is partly because women of the CC genotype had decreased PON1 activity when ingesting a lower ratio of n-6/n-3 diet (P < .05), while women of the TT genotype had increased PON1 activity (P < .05). In conclusion, the overall presence of the C allele was associated with increased serum PON1 activity, although a diet with high saturated fatty acid or a low ratio of n-6/n-3 reduced PON1 activity in women with the CC genotype.

Choline, Its Potential Role in Nonalcoholic Fatty Liver Disease, and the Case for Human and Bacterial Genes.

Our understanding of the impact of poor hepatic choline/phosphatidylcholine availability in promoting the steatosis characteristic of human nonalcoholic fatty liver disease (NAFLD) has recently advanced and possibly relates to phosphatidylcholine/phosphatidylethanolamine concentrations in various, membranes as well as cholesterol dysregulation. A role for choline/phosphatidylcholine availability in the progression of NAFLD to liver injury and serious hepatic consequences in some individuals requires further elucidation. There are many reasons for poor choline/phosphatidylcholine availability in the liver, including low intake, estrogen status, and genetic polymorphisms affecting, in particular, the pathway for hepatic de novo phosphatidylcholine synthesis. In addition to free choline, phosphatidylcholine has been identified as a substrate for trimethylamine production by certain intestinal bacteria, thereby reducing host choline bioavailability and providing an additional link to the increased risk of cardiovascular disease faced by those with NAFLD. Thus human choline requirements are highly individualized and biomarkers of choline status derived from metabolomics studies are required to predict those at risk of NAFLD induced by choline deficiency and to provide a basis for human intervention trials.

Genetic polymorphisms that affect selenium status and response to selenium supplementation in United Kingdom pregnant women.

BACKGROUND: Low selenium status in pregnancy has been associated with a number of adverse conditions. In nonpregnant populations, the selenium status or response to supplementation has been associated with polymorphisms in dimethylglycine dehydrogenase (DMGDH), selenoprotein P (SEPP1) and the glutathione peroxidases [cytosolic glutathione peroxidase (GPx1) and phospholipid glutathione peroxidase (GPx4)]. OBJECTIVE: We hypothesized that, in pregnant women, these candidate polymorphisms would be associated with selenium status in early pregnancy, its longitudinal change, and the interindividual response to selenium supplementation at 60 µg/d. DESIGN: With the use of stored samples and data from the United Kingdom Selenium in Pregnancy Intervention (SPRINT) study in 227 pregnant women, we carried out genetic-association studies, testing for associations between selenium status, its longitudinal change, and response to supplementation and common genetic variation in DMGDH (rs921943), SEPP1 (rs3877899 and rs7579), GPx1 (rs1050450) and GPx4 (rs713041). Selenium status was represented by the concentration of whole-blood selenium at 12 and 35 wk of gestation, the concentration of toenail selenium at 16 wk of gestation, and plasma glutathione peroxidase (GPx3) activity at 12 and 35 wk of gestation. RESULTS: Our results showed that DMGDH rs921943 was significantly associated with the whole-blood selenium concentration at 12 wk of gestation (P = 0.032), which explained ≤2.0% of the variance. This association was replicated with the use of toenail selenium (P = 0.043). In unsupplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in whole-blood selenium from 12 to 35 wk of gestation (P = 0.005), which explained 8% of the variance. In supplemented women, SEPP1 rs3877899 was significantly associated with the percentage change in GPx3 activity from 12 to 35 wk of gestation (P = 0.01), which explained 5.3% of the variance. Selenium status was not associated with GPx1, GPx4, or SEPP1 rs7579. CONCLUSIONS: In agreement with previous studies, we show that the genetic variant rs921943 in DMGDH is significantly associated with selenium status in United Kingdom pregnant women. Notably, our study shows that women who carry the SEPP1 rs3877899 A allele are better able to maintain selenium status during pregnancy, and their GPx3 activity increases more with supplementation, which suggests better protection from low selenium status. The SPRINT study was registered at www.isrctn.com as ISRCTN37927591.

Selenium metabolism to the trimethylselenonium ion (TMSe) varies markedly because of polymorphisms in the indolethylamine N-methyltransferase gene.

BACKGROUND: Selenium is an essential element, but its metabolism in humans is not well characterized. A few small studies indicate that the trimethylselenonium ion (TMSe) is a common selenium metabolite in humans. OBJECTIVE: This study aimed to elucidate the human metabolism of selenium to TMSe. DESIGN: Study individuals constituted subsamples of 2 cohorts: 1) pregnant women (n = 228) and their 5-y-old children (n = 205) in rural Bangladesh with poor selenium status [median urinary selenium (U-Se): 6.4 µg/L in mothers, 14 µg/L in children] and 2) women in the Argentinian Andes (n = 83) with adequate selenium status (median U-Se: 24 µg/L). Total U-Se and blood selenium were measured by inductively coupled plasma mass spectrometry (ICPMS), and urinary concentrations of TMSe were measured by high-performance liquid chromatography/vapor generation/ICPMS. A genomewide association study (GWAS) was performed for 1,629,299 (after filtration) single nucleotide polymorphisms (SNPs) in the Bangladeshi women (n = 72) by using Illumina Omni5M, and results were validated by using real-time polymerase chain reaction. RESULTS: TMSe "producers" were prevalent (approximately one-third) among the Bangladeshi women and their children, in whom TMSe constituted ∼10-70% of U-Se, whereas "nonproducers" had, on average, 0.59% TMSe. The TMSe-producing women had, on average, 2-µg U-Se/L higher concentrations than did the nonproducers. In contrast, only 3 of the 83 Andean women were TMSe producers (6-15% TMSe in the urine); the average percentage among the nonproducers was 0.35%. Comparison of the percentage of urinary TMSe in mothers and children indicated a strong genetic influence. The GWAS identified 3 SNPs in the indolethylamine N-methyltransferase gene (INMT) that were strongly associated with percentage of TMSe (P < 0.001, false-discovery rate corrected) in both cohorts. CONCLUSIONS: There are remarkable population and individual variations in the formation of TMSe, which could largely be explained by SNPs in INMT. The TMSe-producing women had higher U-Se concentrations than did nonproducers, but further elucidation of the metabolic pathways of selenium is essential for the understanding of its role in human health. The MINIMat trial was registered at isrctn.org as ISRCTN16581394.

Genetic variation in FADS genes is associated with maternal long-chain PUFA status but not with cognitive development of infants in a high fish-eating observational study.

Long-chain n-6 and n-3 PUFA (LC-PUFA), arachidonic acid (AA) (20:4n-6) and DHA (22:6n-3), are critical for optimal brain development. These fatty acids can be consumed directly from the diet, or synthesized endogenously from precursor PUFA by Δ-5 (encoded by FADS1) and Δ-6 desaturases (encoded by FADS2). The aim of this study was to determine the potential importance of maternal genetic variability in FADS1 and FADS2 genes to maternal LC-PUFA status and infant neurodevelopment in populations with high fish intakes. The Nutrition Cohorts 1 (NC1) and 2 (NC2) are longitudinal observational mother-child cohorts in the Republic of Seychelles. Maternal serum LC-PUFA was measured at 28 weeks gestation and genotyping for rs174537 (FADS1), rs174561 (FADS1), rs3834458 (FADS1-FADS2) and rs174575 (FADS2) was performed in both cohorts. The children completed the Bayley Scales of Infant Development II (BSID-II) at 30 months in NC1 and at 20 months in NC2. Complete data were available for 221 and 1310 mothers from NC1 and NC2 respectively. With increasing number of rs3834458 minor alleles, maternal concentrations of AA were significantly decreased (NC1 p=0.004; NC2 p<0.001) and precursor:product ratios for linoleic acid (LA) (18:2n-6)-to-AA (NC1 p<0.001; NC2 p<0.001) and α-linolenic acid (ALA) (18:3n-3)-to-DHA were increased (NC2 p=0.028). There were no significant associations between maternal FADS genotype and BSID-II scores in either cohort. A trend for improved PDI was found among infants born to mothers with the minor rs3834458 allele.In these high fish-eating cohorts, genetic variability in FADS genes was associated with maternal AA status measured in serum and a subtle association of the FADS genotype was found with neurodevelopment.

Effect of a 5-mo nutritional intervention on nutritional status and quality of life for patient with 3-hydroxyisobutyryl-coenzyme A hydrolase deficiency: A case report.

3-Hydroxy-isobutyryl-coenzyme A (CoA) hydrolase (HBICH) deficiency is a rare cerebral organic aciduria caused by disturbance of valine catabolism that leads to the accumulation of toxic metabolites, methacrylyl-CoA. The major feature exhibited by a patient with HBICH deficiency includes multiple congenital malformations and abnormal neurologic findings. However, the pathophysiology of this disease remains unknown. The major treatment for HBICH deficiency involves a low-protein diet, especially restricting valine, supplemented with micronutrients and carnitine. To our knowledge, only four patients with HBICH deficiency have been reported. These patients were boys and presented with different clinical, biochemical, and genetic features than our patient. In this report, we described what was to our knowledge the first genetically confirmed girl with HBICH deficiency in China. A 5-mo nutritional intervention was given to the patient by a nutritional support team. On this regimen, the patient's symptoms were alleviated and her quality of life was improved.

Clinical zinc deficiency as early presentation of Wilson disease.

Wilson disease is a rare autosomal recessive disorder of the copper metabolism caused by homozygous or compound heterozygous mutations in the ATP-ase Cu(2+) transporting polypeptide (ATP7B) gene. The copper accumulation in different organs leads to the suspicion of Wilson disease. We describe a child with clinical zinc deficiency as presenting symptom of Wilson disease, which was confirmed by 2 mutations within the ATP7B gene and an increased copper excretion.