-
Stem Cell Research Jun 2023Mutations in the ETFDH gene, encoding electron transfer flavoprotein dehydrogenase, have been identified to cause riboflavin-responsive multiple acyl-CoA dehydrogenase...
Mutations in the ETFDH gene, encoding electron transfer flavoprotein dehydrogenase, have been identified to cause riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD) (Wen et al., 2010). We performed the generation and characterization of human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient with RR-MADD carrying two heterozygous ETFDH mutations (p.D130V and p.A84V). Their pluripotency was verified by the expression of several pluripotency markers on RNA and protein levels and the capability to differentiate into all three germ layers.
Topics: Humans; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Induced Pluripotent Stem Cells; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Mutation; Riboflavin
PubMed: 37019029
DOI: 10.1016/j.scr.2023.103067 -
AJP Reports Jan 2023Total parental nutrition (TPN) is a critical component of neonatal intensive care. Supply shortages leading to deficiencies in TPN constituents can have devastating...
Total parental nutrition (TPN) is a critical component of neonatal intensive care. Supply shortages leading to deficiencies in TPN constituents can have devastating consequences for critically ill patients in the neonatal intensive care unit (NICU), who may be initially misdiagnosed as potential inborn errors of metabolism. Here, we present three cases of patients with prolonged TPN dependence due to intra-abdominal pathology who presented with signs and symptoms concerning for metabolic disorders and who were ultimately determined to be a result of vitamin deficiencies in the TPN after unnecessary testing and interventions had occurred. These diagnostic errors highlight the need for clinicians to maintain a high index of suspicion for nutritional deficiencies when treating patients in the NICU with potential metabolic disorders during times when TPN constituents are not available, as well as advocating to ensure that adequate supplies are maintained for this vulnerable population.
PubMed: 36923230
DOI: 10.1055/a-2032-9737 -
Nutrition Research and Practice Feb 2023In times of disaster, simplified and minimized nutritional standards are necessary for a quick response to provide nutritious relief food. This study aimed to develop...
BACKGROUND/OBJECTIVES
In times of disaster, simplified and minimized nutritional standards are necessary for a quick response to provide nutritious relief food. This study aimed to develop nutrient-based nutritional standards for foodservice at shelters during disasters in the Republic of Korea (South Korea).
SUBJECTS/METHODS
The standards were developed in 2 phases. First, nutrients to be included in the standards were selected. Initial candidates were selected considering 3 aspects: preceding standards, insufficient intake during disasters, and inadequate intake among South Koreans. Final selection was made by excluding nutrients for 3 reasons: nutrients for which there is no deficiency concern in South Korea, nutrients whose intake data were not available, or nutrients whose values presented by Dietary Reference Intakes for Koreans are difficult to achieve based on the current diet among South Koreans. Second, the reference values of energy and the selected nutrients were calculated. The reference values for the entire population who were 1-year-old and over were calculated by multiplying the estimated energy requirements or the recommended nutrient intake and the proportion of each age and sex group. Respective reference values were also calculated for 4 different age groups (1-5, 6-11, 12-64, and ≥ 65-year-old).
RESULTS
The standards for the entire population were 2,000 kcal for energy, 55 g for protein, 650 µg retinol activity equivalents for vitamin A, 95 mg for vitamin C, 1.1 mg for thiamin, 1.3 mg for riboflavin, 14 mg niacin equivalents for niacin, 350 µg dietary folate equivalents for folic acid, 750 mg for calcium, and 11 mg for iron. Four additional standards corresponding to each age group were developed.
CONCLUSIONS
The nutritional standards during disasters were developed for South Korea, including energy and 9 nutrients with reference values for the entire population and 4 different age groups. The standards will contribute to maintaining the health of disaster evacuees in South Korea.
PubMed: 36777808
DOI: 10.4162/nrp.2023.17.1.135 -
Animal Nutrition (Zhongguo Xu Mu Shou... Mar 2023This study was to determine the effects of riboflavin deficiency (RD) on intestinal development, jejunum mucosa proteome, cecal short-chain fatty acids (SCFA) profiling,...
This study was to determine the effects of riboflavin deficiency (RD) on intestinal development, jejunum mucosa proteome, cecal short-chain fatty acids (SCFA) profiling, and cecal microbial diversity and community of starter Pekin ducks. Male white Pekin ducks (1 d old, 240) were allocated into 2 groups, with 12 replicates and 10 birds per replicate in each group. For 21 d, all ducks had ad libitum access to either an RD or a riboflavin adequate (control, CON) diet, formulated by supplementing a basal diet with 0 or 10 mg riboflavin per kg of diet, respectively. Compared to the CON group, growth retardation, high mortality, and poor riboflavin status were observed in the RD group. Furthermore, RD reduced the villus height and the ratio of villus height to crypt depth of jejunum and ileum ( < 0.05), indicating morphological alterations of the small intestine. In addition, dietary RD enhanced relative cecum weight and decreased cecal SCFA concentrations ( < 0.05), including propionate, isobutyrate, butyrate, and isovalerate. The jejunum mucosa proteomics showed that 208 proteins were upregulated and 229 proteins were downregulated in the RD group compared to those in the CON group. Among these, RD mainly suppressed intestinal absorption and energy generation processes such as glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, leading to impaired ATP generation. In addition, RD decreased the community richness and diversity of the bacterial community in the cecum of ducks. Specifically, RD reduced the abundance of butyrate-producing bacteria in the cecum ( < 0.05), such as , and . Dietary RD resulted in growth depression and intestinal hypofunction of Pekin ducks, which could be associated with impaired intestinal absorption and energy generation processes in intestinal mucosa, as well as gut microbiota dysbiosis. These findings contribute to our understanding of the mechanisms of intestinal hypofunction due to RD.
PubMed: 36712406
DOI: 10.1016/j.aninu.2022.09.013 -
Frontiers in Neurology 2022Lipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron...
BACKGROUND
Lipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene cause multiple acyl-CoA dehydrogenase deficiency (MADD), and have a manifestation of LSM. Muscle biopsy helps clarify the diagnosis of LSM, and next-generation sequencing (NGS) can be useful in identifying genomic mutation sites. The diagnosis of MADD contributes to targeted therapy.
CASE PRESENTATION
We report on a teenager who appeared to have muscle weakness and exercise intolerance at the onset. Before the referral to our hospital, he was unsuccessfully treated with glucocorticoid for suspected polymyositis. The next-generation sequencing of the proband and his parents revealed heterozygous variations, c.365G>A (p.G122D) inherited from the father, c.176-194_176-193del, and c.832-316C>T inherited from the mother in the ETFDH gene. The tandem mass spectrometry identified the mutations to be pathogenic. However, his parents and his younger sister who were detected with a mutation of c.365G>A presented no clinical symptoms. This indicates that the combination of the three compound heterozygous mutations in ETFDH is significant. After MADD was diagnosed, a dramatic clinical recovery and biochemical improvement presented as riboflavin was given to the patient across a week, which further confirmed the diagnosis of MADD.
CONCLUSION
Our observations extend the spectrum of ETFDH variants in Chinese the population and reinforce the role of NGS in diagnosis of MADD. Early diagnosis and appropriate treatment of LSM lead to great clinical efficacy and avoid some lethal complications.
PubMed: 36588907
DOI: 10.3389/fneur.2022.991060 -
Brain Sciences Nov 2022(1) Background: Riboflavin transporter deficiency (RTD), formerly known as Brown−Vialetto−Van Laere syndrome, is a rare condition that causes a progressive...
(1) Background: Riboflavin transporter deficiency (RTD), formerly known as Brown−Vialetto−Van Laere syndrome, is a rare condition that causes a progressive neurological syndrome in early life with features of auditory and optic neuropathy, weakness of bulbar muscles and the diaphragm and sensorimotor neuropathy. Pathologic mutations in the genes that code for riboflavin transporters have been identified as the genetic basis of RTD, and the majority of the genetically confirmed cases are caused by mutations of SLC52A3, a riboflavin transporter 2 coding gene or compound mutations in SLC52A2, encoding riboflavin transporter 3. Fatality in childhood is common if the condition is left untreated, but survival into adulthood has been reported in cases treated with high-dose oral riboflavin. (2) Case summary: We report two long-term survivors of RTD type 2 due to compound heterozygous 185T> G and 1258G>A mutations in gene SLC2A2. They are two brothers in a family in which two female siblings died in childhood from a similar neurological disorder. Brother one, the older RTD survivor, is aged 71, and brother two is aged 58. Both have significant visual impairment from optic nerve atrophy and sensory ataxia. Their muscle biopsies showed decreased muscle adenosine monophosphate (AMP) deaminase activity. No AMPD1 mutation was detected through whole-genome sequencing. (3) Conclusion: Co-existing riboflavin transporter deficiency (RTD) type 2 and muscle AMP deaminase deficiency has not been previously reported. Apart from the possibility that there is a milder phenotype associated with these mutations in SLC2A2, AMP deaminase deficiency might have contributed to a survival benefit by preserving muscle function through accumulating intracellular AMP.
PubMed: 36552065
DOI: 10.3390/brainsci12121605 -
NanoImpact Jan 2023Nanoscale Fe containing particles can penetrate the root apoplast. Nevertheless, cell wall size exclusion questions that for Fe mobilisation, a close contact between the...
Nanoscale Fe containing particles can penetrate the root apoplast. Nevertheless, cell wall size exclusion questions that for Fe mobilisation, a close contact between the membrane integrating FERRIC REDUCTASE OXIDASE (FRO) enzymes and Fe containing particles is required. Haematite nanoparticle suspension, size of 10-20 nm, characterized by Fe Mössbauer spectroscopy, TEM, ICP and SAED was subjected to Fe utilisation by the flavin secreting model plant cucumber (Cucumis sativus). Alterations in the structure and distribution of the particles were revealed by Fe Mössbauer spectroscopy, HRTEM and EDS element mapping. Biological utilisation of Fe resulted in a suppression of Fe deficiency responses (expression of CsFRO 1, 2 & 3 and RIBOFLAVIN A1; CsRIBA1 genes and root ferric chelate reductase activity). Haematite nanoparticles were stacked in the middle lamella of the apoplast. Fe mobilisation is evidenced by the reduction in the particle size. Fe release from nanoparticles does not require a contact with the plasma membrane. Parallel suppression in the CsFRO 1&3 and CsRIBA1 transcript amounts support that flavin biosynthesis is an inclusive Fe deficiency response involved in the reduction-based Fe utilisation of Cucumis sativus roots. CsFRO2 is suggested to play a role in the intracellular Fe homeostasis.
Topics: Iron; Cucumis sativus; Oxidoreductases; Biological Transport; Flavins
PubMed: 36470408
DOI: 10.1016/j.impact.2022.100444 -
Frontiers in Nutrition 2022The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with...
The influence of B vitamins on human fertility and infertility treatments remains elusive. Therefore, this study investigated the association of most B vitamins with IVF-ET outcomes. A total of 216 subjects aged <35 year in their first oocyte retrieval cycle were recruited. Blood samples from the participants were collected before the oocyte pick-up procedure, and serum levels of riboflavin, niacin, pantothenic acid, vitamin B6 (including PA and PLP), folate, and methylmalonic acid (MMA) were detected using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Endpoints were classified into three groups according to tertiles (lower, middle, and upper) of each vitamin index, and the association of the serum vitamin status with intermediate and clinical outcomes was analyzed using a generalized estimating equation model. Higher riboflavin levels were associated with elevated probabilities of high-quality embryos, as well as clinical pregnancy after embryo transfer. A greater likelihood of transferable embryos was found in the middle tertile of serum folate. Similarly, a negative correlation of serum MMA, a marker of vitamin B12 deficiency, with high-quality embryos was identified. No significance was observed for other vitamins in terms of all endpoints. Therefore, sufficient levels of pre-conception riboflavin, folate, and vitamin B12 are recommended for successful infertility treatment and pregnancy planning; further evidence is needed to confirm our conclusion.
PubMed: 36438768
DOI: 10.3389/fnut.2022.962212 -
Molecular Genetics and Metabolism... Dec 2022Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disease caused by a defect in electron transfer flavoprotein alpha (ETFA), ETF beta (ETFB),...
Clinical and molecular investigation of 37 Japanese patients with multiple acyl-CoA dehydrogenase deficiency: p.Y507D in , a common Japanese variant, causes a mortal phenotype.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disease caused by a defect in electron transfer flavoprotein alpha (ETFA), ETF beta (ETFB), or ETF dehydrogenase (ETFDH), and riboflavin metabolism disorders have recently been reported to present as mimicking MADD. MADD is roughly classified into neonatal (type 1 or 2) and later-onset (type 3) forms. To identify clinicogenetic characteristics in Japan, we investigated 37 Japanese patients with MADD diagnosed from 1997 to 2020. The causes of MADD were ETFDH deficiency in 26 patients, ETFA deficiency in four, ETFB deficiency in six, and riboflavin metabolism disorder in one. All 15 patients with the neonatal-onset type died by 2 years of age, while five of 22 patients with the later-onset form died by 3 years of age. Furthermore, 8 of 15 patients with the later-onset form of ETFDH deficiency treated with riboflavin were riboflavin non-responders. p.Y507D in was identified as the most common variant (9 of 48 alleles, 18.8%). Of two patients with a homozygous p.Y507D variant, one experienced disease onset and died in the neonatal period, while the other experienced disease onset at two months of age and died at two years old, suggesting that the p.Y507D variant results in fatal outcomes. Our study concluded that more than half of Japanese patients with MADD died by three years old, and more than half of patients with the later-onset form had poor responsiveness to riboflavin, partly due to the unique Japanese p.Y507D variant in .
PubMed: 36406819
DOI: 10.1016/j.ymgmr.2022.100940