-
Mitochondrion May 2024Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented...
Pathogenic ACAD9 variants cause complex I deficiency. Patients presenting in infancy unresponsive to riboflavin have high mortality. A six-month-old infant presented with riboflavin unresponsive lactic acidosis and life-threatening cardiomyopathy. Treatment with high dose bezafibrate and nicotinamide riboside resulted in marked clinical improvement including reduced lactate and NT-pro-brain type natriuretic peptide levels, with stabilized echocardiographic measures. After a long stable period, the child succumbed from cardiac failure with infection at 10.5 months. Therapy was well tolerated. Peak bezafibrate levels exceeded its EC. The clinical improvement with this treatment illustrates its potential, but weak PPAR agonist activity of bezafibrate limited its efficacy.
PubMed: 38797357
DOI: 10.1016/j.mito.2024.101905 -
Frontiers in Pediatrics 2024Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter...
BACKGROUND
Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter genes SLC52A2 and SLC52A3. BVVL syndrome has a variable age of presentation, and it is characterized by progressive auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise secondary to diaphragmatic and vocal cord paralysis. BVVL syndrome has a poor prognosis in the absence of treatment, including morbidity with quadriparesis and sensorineural hearing loss, with mortality in the younger age group. Early administration of riboflavin is associated with prolonged survival, low morbidity, and reversal of some clinical manifestations.
CASE PRESENTATION
We describe an 18-month-old male infant with progressive pontobulbar palsy, loss of developmental milestones, and a clinical picture suggestive of chronic inflammatory demyelinating neuropathy. A nerve conduction study revealed axonal neuropathy, while molecular analysis revealed a homozygous mutation in one of the riboflavin transporter genes, SLC52A3, confirming BVVL syndrome. The patient needed long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he experienced moderate recovery of motor function.
CONCLUSION
This report highlights the importance of considering BVVL syndrome in any patient who presents with the clinical phenotype of pontobulbar palsy and peripheral axonal neuropathy, as early riboflavin treatment may improve or halt disease progression, thus reducing the associated mortality and morbidity.
PubMed: 38745833
DOI: 10.3389/fped.2024.1377515 -
Journal of Clinical Medicine Feb 2024Obesity is a prevalent condition associated with various comorbidities, impacting mortality, fertility, and quality of life. Its relationship with type 2 diabetes...
Obesity is a prevalent condition associated with various comorbidities, impacting mortality, fertility, and quality of life. Its relationship with type 2 diabetes mellitus (DMII) is well established, with nearly 44% prevalence. Bariatric surgery has proven crucial for treating both obesity and DMII. The comparison between surgical techniques, such as sleeve gastrectomy (SG) and one anastomosis gastric bypass (OAGB), remains controversial in terms of glycemic control efficacy. This retrospective study aimed to assess DMII remission efficacy between SG and OAGB after 36 months. From January 2016 to September 2020, 201 patients who underwent SG and OAGB for morbid obesity associated with DMII were accurately followed-up with for 36 months, focusing on %HbA1c, DMII remission, anthropometric results, and nutrient deficiency. Although DMII remission did not exhibit statistical significance between the groups (82% vs. 93%, SG vs. OAGB, = 0.051), OAGB demonstrated a more robust association with glycemic control (Odds Ratio 0.51) throughout the entire follow-up and yielded superior anthropometric outcomes. Notably, nutrient deficiencies, excluding cholecalciferol, iron, and riboflavin, did not show significant intergroup differences. This study contributes valuable insights into the extended-term efficacy of SG and OAGB in DMII remission. The nuanced findings underscore the multifaceted nature of metabolic outcomes, suggesting that factors beyond weight loss influence diabetes resolution. Larger comparative studies are warranted to comprehensively address this issue.
PubMed: 38337593
DOI: 10.3390/jcm13030899 -
The ISME Journal Jan 2024The endosymbiosis between the pathogenic fungus Rhizopus microsporus and the toxin-producing bacterium Mycetohabitans rhizoxinica represents a unique example of host...
The endosymbiosis between the pathogenic fungus Rhizopus microsporus and the toxin-producing bacterium Mycetohabitans rhizoxinica represents a unique example of host control by an endosymbiont. Fungal sporulation strictly depends on the presence of endosymbionts as well as bacterially produced secondary metabolites. However, an influence of primary metabolites on host control remained unexplored. Recently, we discovered that M. rhizoxinica produces FO and 3PG-F420, a derivative of the specialized redox cofactor F420. Whether FO/3PG-F420 plays a role in the symbiosis has yet to be investigated. Here, we report that FO, the precursor of 3PG-F420, is essential to the establishment of a stable symbiosis. Bioinformatic analysis revealed that the genetic inventory to produce cofactor 3PG-F420 is conserved in the genomes of eight endofungal Mycetohabitans strains. By developing a CRISPR/Cas-assisted base editing strategy for M. rhizoxinica, we generated mutant strains deficient in 3PG-F420 (M. rhizoxinica ΔcofC) and in both FO and 3PG-F420 (M. rhizoxinica ΔfbiC). Co-culture experiments demonstrated that the sporulating phenotype of apo-symbiotic R. microsporus is maintained upon reinfection with wild-type M. rhizoxinica or M. rhizoxinica ΔcofC. In contrast, R. microsporus is unable to sporulate when co-cultivated with M. rhizoxinica ΔfbiC, even though the fungus was observed by super-resolution fluorescence microscopy to be successfully colonized. Genetic and chemical complementation of the FO deficiency of M. rhizoxinica ΔfbiC led to restoration of fungal sporulation, signifying that FO is indispensable for establishing a functional symbiosis. Even though FO is known for its light-harvesting properties, our data illustrate an important role of FO in inter-kingdom communication.
Topics: Symbiosis; Rhizopus; Spores, Fungal; Flavins; CRISPR-Cas Systems; Riboflavin
PubMed: 38691425
DOI: 10.1093/ismejo/wrae074 -
Molecular Genetics and Metabolism... Mar 2024Riboflavin transporter deficiency (RTD) is a neurodegenerative disorder that presents from infancy to adulthood with a progressive axonal neuropathy characterized by a...
Riboflavin transporter deficiency (RTD) is a neurodegenerative disorder that presents from infancy to adulthood with a progressive axonal neuropathy characterized by a variety of neurologic symptoms including hearing loss, weakness, bulbar palsy, and respiratory insufficiency. Pathogenic variants in and are implicated in the pathogenesis of RTD type 2 and 3, respectively. Early identification of this disorder is critical, as it is treatable with riboflavin supplementation. We describe a 16-year-old female with a phenotype consistent with RTD3 found to have a novel heterozygous variant. Though RTD is typically considered an autosomal recessive condition, her heterozygous variant was thought to be disease causing after further genetic analysis and given her improvement in response to riboflavin supplementation. This case highlights the importance of reinterpretation of genetic testing, particularly when there is a high clinical suspicion for disease.
PubMed: 38469093
DOI: 10.1016/j.ymgmr.2024.101051 -
Voprosy Pitaniia 2024Despite the widespread use of oat β-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and...
Despite the widespread use of oat β-glucans as ingredient of foods and dietary supplements, there is insufficient data on their effect on the metabolism of vitamins and minerals. of the study was to evaluate the effect of including oat bran with a high content of β-glucans (β-glucan) in the diet on the absorption of micronutrients and lipid metabolism in growing rats deficient in vitamins D, group B and trace elements (iron, copper, zinc). . After the development of micronutrient deficiency (for 23 days), in order to assess the effect of oat bran (5%) with a high content of β-glucans on the correction of the micronutrient status of growing male Wistar rats (with initial body weight of 70.7±0.7 g), the missing micronutrients were introduced in the semi-synthetic diet deficient in vitamins D, group B, iron, copper and zinc within 7 days either along with β-glucan (1.47%) or without its addition. Indicators of micronutrient sufficiency (riboflavin serum concentration, daily urinary excretion of thiamine, riboflavin and 4-pyridoxic acid, measured by fluorometric methods; serum concentration and urinary excretion of calcium, magnesium, iron, zinc, copper, phosphorus, measured by the atomic absorption method or using standard methods on a biochemical analyzer) and the biochemical parameters of blood serum were compared with the parameters of rats adequately provided with all micronutrients throughout the experiment. . Replenishment of missing micronutrients in the diet of rats with deficiency in vitamins D and group B, iron, copper and zinc for 7 days led to the elimination of deficiency of vitamins B1, B2 and B6, regardless of the presence of β-glucans in the diet. At the same time, against the background of the presence of β-glucans in the feed, an increase in the absorption of iron was observed, as evidenced by an increase by 1.73 times in iron blood plasma level (р<0.05) and a tendency towards its urinary excretion decrease by 1.60 fold (р<0.10) compared to animals from the control group. Adding oat bran with β-glucans to the feed did not lead to a decrease in blood plasma level of total cholesterol and low-density lipoproteins cholesterol. The levels of high-density lipoprotein cholesterol and triglycerides in rats of all three groups did not have statistically significant differences. . The presence of β-glucans in the diet had virtually no effect on the absorption of B vitamins and improved the absorption of iron.
Topics: Male; Rats; Animals; Vitamin B Complex; Avena; Copper; Lipid Metabolism; Rats, Wistar; Minerals; Trace Elements; Thiamine; Diet; Riboflavin; Micronutrients; Iron; Zinc; Cholesterol; beta-Glucans
PubMed: 38555611
DOI: 10.33029/0042-8833-2024-93-1-72-79 -
Food Chemistry Sep 2024B-group vitamins are important micronutrients for maintaining human health; nevertheless, B vitamin deficiency is a globally widespread issue. Thus, it is relevant to...
B-group vitamins are important micronutrients for maintaining human health; nevertheless, B vitamin deficiency is a globally widespread issue. Thus, it is relevant to accurately assess the B-vitamin content in staple crop products such as wheat grains. Here, we developed a multi-enzyme extraction method allowing accurate quantification of seven B vitamins in wheat using ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Free forms of thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7) and folates (B9) were determined with recoveries ranging from 81 to 118% and accuracy below 15% bias. The precision was below 20% relative standard deviation and the internal standards adequately compensated for matrix effects. The method was applied to determine the B vitamin stabilities in wheat grains stored at different temperatures and periods. The results provide an important basis in future studies aiming at understanding nutritional availability of B vitamins.
Topics: Triticum; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Vitamin B Complex
PubMed: 38776794
DOI: 10.1016/j.foodchem.2024.139667 -
Frontiers in Microbiology 2023Insect-microbe endosymbiotic associations are omnipresent in nature, wherein the symbiotic microbes often play pivotal biological roles for their host insects. In...
Insect-microbe endosymbiotic associations are omnipresent in nature, wherein the symbiotic microbes often play pivotal biological roles for their host insects. In particular, insects utilizing nutritionally imbalanced food sources are dependent on specific microbial symbionts to compensate for the nutritional deficiency via provisioning of B vitamins in blood-feeding insects, such as tsetse flies, lice, and bedbugs. Bat flies of the family Nycteribiidae (Diptera) are blood-sucking ectoparasites of bats and shown to be associated with co-speciating bacterial endosymbiont " Aschnera chinzeii," although functional aspects of the microbial symbiosis have been totally unknown. In this study, we report the first complete genome sequence of from the bristled bat fly . The genome consisted of a 748,020 bp circular chromosome and a 18,747 bp circular plasmid. The chromosome encoded 603 protein coding genes (including 3 pseudogenes), 33 transfer RNAs, and 1 copy of 16S/23S/5S ribosomal RNA operon. The plasmid contained 10 protein coding genes, whose biological function was elusive. The genome size, 0.77 Mbp, was drastically reduced in comparison with 4-6 Mbp genomes of free-living γ-proteobacteria. Accordingly, the genome was devoid of many important functional genes, such as synthetic pathway genes for purines, pyrimidines, and essential amino acids. On the other hand, the genome retained complete or near-complete synthetic pathway genes for biotin (vitamin B7), tetrahydrofolate (vitamin B9), riboflavin (vitamin B2), and pyridoxal 5'-phosphate (vitamin B6), suggesting that provides these vitamins and cofactors that are deficient in the blood meal of the host bat fly. Similar retention patterns of the synthetic pathway genes for vitamins and cofactors were also observed in the endosymbiont genomes of other blood-sucking insects, such as of human lice, of louse flies, and of tsetse flies, which may be either due to convergent evolution in the blood-sucking host insects or reflecting the genomic architecture of -allied bacteria.
PubMed: 38318130
DOI: 10.3389/fmicb.2023.1336919 -
Journal of Pharmaceutical and... Apr 2024B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique...
A novel automated multi-cycle magnetic solid-phase extraction coupled to LC-MS/MS to study the disorders of six functional B vitamins in patients with gastroenterology and hyperhomocysteinemia.
B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique for determining multiple B vitamins, however, their complexity in real biological matrices makes it hard to achieve satisfactory recovery and accuracy when simultaneous detection. In this study, a novel automated multi-cycle magnetic SPE (MSPE) coupled to the LC-MS/MS method was established using a mixed-mode anion exchange magnetic adsorbent for the simultaneous extraction of six functional B vitamins, including methylmalonic acid, riboflavin, pantothenic acid, 4-pyridoxic acid, folic acid, and 5-methyltetrahydrofolate. After three consecutive MSPE cycles, the recoveries of all analytes were between 51.5% and 89.6%. The method exhibited excellent sensitivity and linearity, with a dynamic range of 200-fold (R > 0.99 for all analytes), exceptional accuracy (ranging between 95.4% and 105.6%) and precision (with RSDs ≤ 6.2%) without significant matrix effects or interferences. Compared to manual SPE method, the automated multi-cycle MSPE method has better feasibility and greater vitamin coverage. It shows a high correlation with the manual method for the detection of 5-methyltetrahydrofolate and folate (R > 0.99). A study of patients from the gastroenterology department showed that those undergoing surgery and those with malignancies may be at risk of folate deficiency. In addition, patients with hyperhomocystinemia had higher levels of methylmalonic acid and lower levels of 5-methyltetrahydrofolate, which correlated with homocysteine levels (R = 0.404 and -0.311, respectively) and showed dose-response relationships. This method is highly automated and cost-effective, with minimal systematic error, making it suitable for the analysis of clinical samples.
Topics: Humans; Chromatography, Liquid; Vitamin B Complex; Liquid Chromatography-Mass Spectrometry; Gastroenterology; Hyperhomocysteinemia; Methylmalonic Acid; Tandem Mass Spectrometry; Vitamin A; Folic Acid; Solid Phase Extraction; Magnetic Phenomena; Chromatography, High Pressure Liquid
PubMed: 38271858
DOI: 10.1016/j.jpba.2024.115989 -
BMJ Case Reports Mar 2024Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder which typically manifests with muscle weakness. However, despite late-onset MADD...
Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder which typically manifests with muscle weakness. However, despite late-onset MADD being treatable, it is often misdiagnosed, due in part to the heterogeneity of presentations. We report a case of late-onset MADD manifesting first as a sensory neuropathy before progressing to myopathic symptoms and acute metabolic decompensation. Early diagnostic workup with acylcarnitine profiling and organic acid analysis was critical in patient outcome; metabolic decompensation and myopathic symptoms were completely reversed with riboflavin supplementation and dietary modification, although sensory neuropathy persisted. Clinical consideration of MADD as part of the differential diagnosis of neuropathy with myopathy is crucial for a timely diagnosis and treatment of MADD.
Topics: Humans; Acyl-CoA Dehydrogenase; Mutation; Electron-Transferring Flavoproteins; Peripheral Nervous System Diseases; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Riboflavin; Rare Diseases
PubMed: 38490702
DOI: 10.1136/bcr-2023-259192