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A Novel Ornithine Aminotransferase Splice Site Mutation Causes Vitamin B6-Responsive Gyrate Atrophy.Journal of Ophthalmic & Vision Research 2024Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the...
PURPOSE
Gyrate atrophy of the choroid and retina (GACR) is a rare congenital disorder and mutations in the ornithine aminotransferase (OAT) gene has been specified as the underlying cause. Patients show a high level of ornithine in body fluids which may be controlled by low protein diets. Pyridoxine (vitamin B6) supplementation may also be effective, however, most patients appear to be nonresponsive to this modality of treatment.
CASE REPORT
Here, we report a characterized case of a vitamin B6-responsive GACR who had a splicing mutation in the gene. The GACR diagnosis was confirmed through the clinical features, imaging, biochemical findings, and whole-exome sequencing (WES) results. WES data revealed the splicing mutation in intron 4 of the gene (NM_001322967: c.425-1GA).
CONCLUSION
Our knowledge about the diagnosis and treatment of GACR can be improved by identifying novel mutations in the gene and accurate follow-up of the patients to determine how they respond to treatment.
PubMed: 38638626
DOI: 10.18502/jovr.v19i1.15446 -
Nutrients Mar 2024Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B-vitamins. The objective was to assess the association of beef...
Beef is an important source of high-quality protein and several micronutrients, including iron, zinc, and B-vitamins. The objective was to assess the association of beef intake with nutrient intake and adequacy among pregnant and lactating women using 24-h dietary recall data. Usual intakes from foods were determined with the National Cancer Institute (NCI) method and % population below Estimated Average Requirement (EAR) or above Adequate Intake (AI) were estimated. A high proportion of pregnant and lactating women had inadequate intakes for vitamin D (94%), vitamin E (82%), vitamin C (52%), and vitamin A (50%), magnesium (35%), folate (31%), zinc (25%), and vitamin B (22%); only 4% and 35% met AI for choline and potassium, respectively. About 67% of pregnant and lactating women were beef consumers, consuming 49 g beef/day. Beef consumers had higher intakes ( < 0.05) of energy, protein, calcium, iron, phosphorus, selenium, sodium, zinc, thiamin, riboflavin, and niacin, and a higher proportion ( < 0.05) met nutrient recommendations for protein, calcium, iron, zinc, thiamin, riboflavin, niacin, vitamin B, and vitamin B compared to non-consumers. In conclusion, pregnant and lactating women generally have inadequate nutrient intakes from their diets. Beef consumers have higher intakes and adequacy for certain nutrients, many of which are inherently available in beef or in foods eaten with beef.
Topics: Animals; Pregnancy; Cattle; Female; Humans; Niacin; Calcium; Lactation; Nutrition Surveys; Nutrients; Eating; Vitamins; Pyridoxine; Riboflavin; Thiamine; Vitamin B 6; Iron; Zinc
PubMed: 38613015
DOI: 10.3390/nu16070981 -
Genetics and Molecular Biology 2024Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an...
Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an adult patient, born to a related couple (third degree cousins), referred for genetic evaluation due to ectopia lentis, deafness and previous diagnosis of juvenile idiopathic arthritis. He was biochemically diagnosed as having Classic Homocystinuria (HCU); Sanger sequencing of the CBS gene showed the genotype NM_000071.2(CBS):c.[833T>C];[833T>C], compatible with the diagnosis of pyridoxine-responsive HCU. As he also had symptoms not usually associated with HCU, exome sequencing was performed. In addition to the variants found in the Sanger sequencing, the following variants were identified: NM_001256317.1(TMPRSS3):c.[413C>A];[413C>A]; and the NM_005807.6(PRG4):c.[3756dup]:[3756dup], confirming the diagnosis of autosomal recessive nonsyndromic deafness and Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome (CACP), respectively. Genomic analysis allowed the refinement of the diagnosis of a complex case and improvement of the patient's treatment.
PubMed: 38593426
DOI: 10.1590/1678-4685-GMB-2022-0335 -
Science Advances Apr 2024Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with mutation still suffer...
Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with mutation still suffer from intellectual disability. It points to a need for additional therapeutic interventions for PDE beyond pyridoxine treatment, which provokes us to investigate the mechanisms underlying the impairment of brain hemostasis by ALDH7A1 deficiency. In this study, we show that ALDH7A1-deficient mice with seizure control exhibit altered adult hippocampal neurogenesis and impaired cognitive functions. Mechanistically, ALDH7A1 deficiency leads to the accumulation of toxic lysine catabolism intermediates, α-aminoadipic-δ-semialdehyde and its cyclic form, δ-1-piperideine-6-carboxylate, which in turn impair de novo pyrimidine biosynthesis and inhibit NSC proliferation and differentiation. Notably, supplementation of pyrimidines rescues abnormal neurogenesis and cognitive impairment in ALDH7A1-deficient adult mice. Therefore, our findings not only define the important role of ALDH7A1 in the regulation of adult hippocampal neurogenesis but also provide a potential therapeutic intervention to ameliorate the defective mental capacities in PDE patients with seizure control.
Topics: Humans; Animals; Mice; Pyridoxine; Aldehyde Dehydrogenase; Seizures; Pyrimidines; Cognition; Epilepsy; 2-Aminoadipic Acid
PubMed: 38579001
DOI: 10.1126/sciadv.adl2764 -
Journal of Gynecology Obstetrics and... Jun 2024This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation... (Comparative Study)
Comparative Study Review
This systematic review aims to evaluate the efficacy and safety of Pyridoxine compared to Dopaminergic agonists (cabergoline and bromocriptine) in post-partum lactation inhibition. Cochrane Central, PubMed/MEDLINE, Cochrane Central, ScienceDirect, ClinicalTrials.gov, Web of Science, CINAHL and Google Scholar, covering the period from inception to November 2023. Additionally, the bibliographies of included articles and previous meta-analyses were screened for any relevant articles. The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The outcomes of interest encompassed inhibition of lactation, breast pain/tenderness, breast engorgement, milk secretion, fever, mastitis, prolactin level and adverse events related to pyridoxine, cabergoline and bromocriptine. Methodological quality assessment was conducted using the Cochrane risk of bias assessment tool for rigorous evaluation. Three clinical trials assessed the effectiveness of pyridoxine and dopaminergic agents (cabergoline and bromocriptine) for lactation inhibition. It was assessed by using different assessment methods such as a scale for milk secretion, serum prolactin levels, and questionnaires for assessing breast engorgement, breast pain, and milk leakage. On the global assessment of the therapeutic efficacy of dopaminergic agents, it was found that there was significant inhibition of lactation as compared to pyridoxine (p < 0.001). In conclusion, this systematic review contributes significant insights into lactation inhibition interventions. Dopaminergic agonists, specifically cabergoline and bromocriptine, stand out as more effective and tolerable choices compared to Pyridoxine. These findings provide a foundation for informed clinical decisions and underscore the need for careful consideration of lactation inhibition strategies in diverse clinical contexts.
Topics: Humans; Bromocriptine; Female; Pyridoxine; Cabergoline; Dopamine Agonists; Lactation; Lactation Disorders; Clinical Trials as Topic
PubMed: 38554942
DOI: 10.1016/j.jogoh.2024.102783 -
Sleep Science (Sao Paulo, Brazil) Mar 2024Obstructive sleep apnea syndrome (OSAS) is characterized by episodic cessations of breathing due to upper airway obstruction during sleep, which may cause...
Obstructive sleep apnea syndrome (OSAS) is characterized by episodic cessations of breathing due to upper airway obstruction during sleep, which may cause disturbances in dietary patterns resulting from appetite-related hormonal changes. The aim of the present study was to investigate the relationship between OSAS and nutritional and dietary patterns. A total of 20 female and 53 male OSAS patients aged > 30 years were enrolled. Demographic data, as well as data on smoking and alcohol habits, were noted, anthropometric measures were made, and a questionnaire regarding chronic diseases including OSAS and four questionnaires on recent food intake frequency and content of nutrition were filled out. The content of nutrition was noted under seven categories: meat, legumes, milk and dairy products, fruits and vegetables, bread and cereals, fat and carbohydrates, and beverages. The severity of OSAS (assessed by the apnea-hypopnea index. AHI) was positively correlated with the body mass index (BMI), the circumferences of the waist, chest, and buttocks, and, in males, with the circumference of the neck as well. There was no correlation between the AHI and nutritional habits in terms of the frequency of meals or snacks, the scores on the Snoring, Tiredness, Observed Apnea, and High Blood Pressure-Body Mass Index, Age, Neck Circumference, and Gender (STOP-BANG) Questionnaire and the corresponding macro- and micronutrients. Worsening apnea scores led to increased intake of macronutrients of carbohydrate and protein and micronutrients of niacin and pyridoxine ( < 0.05), and decreased intake of fat ( < 0.05). The present study demonstrated an association between OSAS severity and recent food intake, manifested in increased intake of carbohydrates, niacin, and pyridoxine, and decreased fat intake.
PubMed: 38545237
DOI: 10.1055/s-0043-1776745 -
International Journal of Molecular... Mar 2024Currently, scientists are increasingly focusing on utilizing the natural flora of the planet to search for and isolate individual bioactive substances that prevent...
Currently, scientists are increasingly focusing on utilizing the natural flora of the planet to search for and isolate individual bioactive substances that prevent various diseases, contribute to increased life expectancy, and affect all major life-supporting systems in the human body. This study describes the examination of the composition of plant raw materials from the Siberian Federal District. The research focuses on plant specimens from the root parts of and , collected in the Kemerovo region. The study determines the contents of the water-soluble vitamins B and C in the research subjects. The investigation includes assessing antioxidant properties, antimicrobial activity, and flavonoid content in extracts based on plant raw materials. All samples show a high percentage of antioxidant activity, with the highest antioxidant activity for at 85.51 and that for at 88.97. The results indicate low antimicrobial activity against (growth inhibition zone up to 15.5 mm). Plant extracts contain significant amounts of B-group vitamins, with pyridoxine in (156.40 μg/mL) and thiamine (46.20 μg/mL) and pyridoxine (357.10 μg/mL) in . Flavonoids (rutin and quercetin) are identified in and extracts based on the study results.
Topics: Humans; Antioxidants; Arctium; Taraxacum; Pyridoxine; Plant Extracts; Vitamins; Anti-Infective Agents
PubMed: 38542237
DOI: 10.3390/ijms25063263 -
International Journal of Molecular... Mar 2024Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B, hold significant importance in both biology and medicine. They facilitate... (Review)
Review
Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B vitamers. However, for those depending on vitamin B as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms.
Topics: Humans; Infant, Newborn; Oxidoreductases; Phosphates; Pyridoxaminephosphate Oxidase; Pyridoxal Phosphate; Vitamin B 6; Pyridoxine; Metabolic Diseases; Vitamins
PubMed: 38542149
DOI: 10.3390/ijms25063174 -
Life (Basel, Switzerland) Feb 2024Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects....
Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects. To overcome DOX limitations, two novel pyridoxine-derived doxorubicin derivatives were synthesized (DOX-1 and DOX-2). In the present study, their antitumor activity and mechanism of action were investigated. Of these two compounds, DOX-2, in which the pyridoxine fragment is attached to the doxorubicin molecule via a C3 linker, revealed higher selectivity against specific cancer cell types compared to doxorubicin and a promising safety profile for conditionally normal cells. However, the compound with a C1 linker (DOX-1) was not characterized by selectivity of antitumor action. It was revealed that DOX-2 obstructs cell cycle progression, induces apoptosis via the mitochondrial pathway without the development of necrosis, and showcases antioxidant capabilities, underlining its cell-regulatory roles. In contrast to doxorubicin's DNA-centric mechanism, DOX-2 does not interact with nuclear DNA. Given these findings, DOX-2 presents a new promising direction in cancer therapeutics, which is deserving of further in vivo exploration.
PubMed: 38541608
DOI: 10.3390/life14030282 -
Scientific Reports Mar 2024Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising...
Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.
Topics: Humans; Malaria, Vivax; Metabolomics; Malaria; Metabolome; Antimalarials
PubMed: 38538661
DOI: 10.1038/s41598-024-54231-5