Pyridoxine Treatment Research Articles

Imerslund-Gräsbeck syndrome in a child with a novel compound heterozygous mutations in the AMN gene: a case report

BackgroundImerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition.Case presentationIn this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS.ConclusionsIn this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy.

Metagenomic and transcriptome insights into the disease resistance mechanisms in fresh-cut apple under pyridoxine treatment

Microbial spoilage poses a significant challenge to fresh-cut apples during storage, impacting quality and consumer health. This study explores pyridoxine’s (vitamin B6; VB6) potential mode of action to mitigate microbial spoilage in fresh-cut apples through physiological, transcriptomic, and metagenomic analysis. VB6 notably reduces microbial spoilage at room temperature by suppressing bacterial genera (Pseudomonas, Curtobacterium, Frigoribacterium) and fungal genera (Alternaria, Penicillium, Aureobasidium, Pseudogymnoascus) proliferation. Spoilage-causing identified biomarkers include species related to Pseudomonas, Curtobacterium, Frigoribacterium, and Penicillium. KEGG analysis suggests correlations of induced disease resistance with tropane alkaloids biosynthesis, plant-pathogen interaction, and phenylpropanoid biosynthesis pathways in fresh-cut apples. Moreover, VB6 treatment enhanced the antioxidant system via maintaining higher total phenolic contents, total flavonoid contents, and ascorbic acid under elevated catalase, superoxide dismutase, and ascorbate peroxidase enzymes activities, induced disease resistance under higher enzymes activities including phenylalanine ammonialyase, chitinase, cinnamate 4-hydroxylase, β-1,3-glucanase, and 4-coumarate: co-enzyme A ligase enzymes activities, maintained elevated VB6 contents, and reduced H2O2 accumulation. Notably, 6 elevated transcription factors involving WRKY, NAC and MYB might regulate disease resistance pathways in fresh-cut apples under VB6 treatment. This research establishes a theoretical and practical foundation for preserving post-processing quality of fresh-cut apples by restraining microbial proliferation through the proposed VB6-induced disease resistance regulatory mechanism.

Dietary vitamin B6 supplementation alleviates heat stress-induced intestinal barrier impairment by regulating the gut microbiota and metabolites in broilers

Heat stress (HS) brings great challenges to the poultry industry. Vitamin B6 (VB6) is an essential micro-nutrient for animals to maintain normal physiological functions and possesses antioxidant and anti-inflammatory properties. This study aimed to explore the effect of VB6 on alleviating HS-induced intestinal barrier impairment in broilers. A total of 250 broilers (609.76 ± 0.34 g) were randomly allocated to 5 groups with 5 replicate cages of 10 birds each. The broilers in thermoneutral (TN) group were raised in thermoneutral conditions (23 ± 1°C) and fed with a basal diet. The birds in other four groups were housed under cycle high temperature (34 ± 1°C for 8 h/d) from d 21 to 35 and fed with the basal diet (HS group) or basal diet supplemented with 6, 12, or 24 mg/kg VB6 (HB-6, HB-12, HB-24 groups). The results showed that HS reduced the growth performance, increased ileum inflammatory cytokines levels, and impaired the gut barrier function (P < 0.05). Compared to the HS group, final body weight, average daily gain, and average daily feed intake, and the feed conversion ratio were improved by VB6 supplementation. The diamine oxidase, interleukin (IL)-1β, tumor necrosis factor-α, IL-18, IL-10, and interferon-γ levels were reduced by VB6 supplementation (P < 0.05). Moreover, VB6 supplementation linearly or quadratically enhanced villus height and villus height-to-crypt depth ratio of duodenum and jejunum, and decreased crypt depth of duodenum and ileum. The mRNA expression of Occlaudin, ZO1, Mucin2, Mucin4, E-cadhein, and β-catenin were increased by VB6 treatment (P < 0.05). Furthermore, dietary VB6 altered the diversity and community of gut microbiota (P < 0.05). A total of 83 differential metabolites associated with the amelioration of VB6 were identified, which were primarily enriched in glycerophospholipid metabolism, caffeine metabolism, and glutathione metabolism pathway. Collectively, VB6 may improve the growth performance and intestinal barrier function of heat-stressed broilers by regulating the ileal microbiota and metabolic homeostasis.

Insights into the Cardioprotective Effects of Pyridoxine Treatment in Diabetic Rats: A Study on Cardiac Oxidative Stress, Cardiometabolic Status, and Cardiovascular Biomarkers.

The aims of this study were to examine the effects of pyridoxine administration on the activities of cardiac antioxidant stress enzymes superoxide dismutase (SOD) and catalase (CAT) and enzyme indicators of cardiometabolic status, lactate and malate dehydrogenase (LDH, MDH), as well as LDH and MDH isoforms' distribution in the cardiac tissue of healthy and diabetic Wistar male rats. Experimental animals were divided into five groups: C1-control (0.9% sodium chloride-NaCl-1 mL/kg, intraperitoneally (i.p.), 1 day); C2-second control (0.9% NaCl 1 mL/kg, i.p., 28 days); DM-diabetes mellitus (streptozotocin 100 mg/kg in 0.9% NaCl, i.p., 1 day); P-pyridoxine (7 mg/kg, i.p., 28 days); and DM + P-diabetes mellitus and pyridoxine (streptozotocin 100 mg/kg, i.p., 1 day and pyridoxine 7 mg/kg, i.p., 28 days). Pyridoxine treatment reduced CAT and MDH activity in diabetic rats. In diabetic rats, the administration of pyridoxine increased LDH1 and decreased LDH4 isoform activities, as well as decreased peroxisomal MDH and increased mitochondrial MDH activities. Our findings highlight the positive effects of pyridoxine administration on the complex interplay between oxidative stress, antioxidant enzymes, and metabolic changes in diabetic cardiomyopathy.

Modulatory effect of vitamin B6 on sex hormone receptors, thyroid, and kisspeptin/kiss1r system in the uterus of pseudopregnant bitches.

This study evaluated whether the treatment of pseudopregnancy in bitches with vitamin B6 modulates uterine expression of receptors for progesterone (PR), oestrogen (ERα), androgen (AR), thyroid hormone (TRα) and the kisspeptin/Kiss1r system. Eighteen pseudopregnant bitches were treated for 20 days in groups receiving placebo (n = 6); cabergoline (5 μg/kg/day; n = 6); or vitamin B6 (50 mg/kg/day; n = 6). Blood was collected on the 1st day of drug administration and 120 h later to measure serum prolactin (PRL). After treatment, they were ovariohysterectomized and uterine fragments were collected for histomorphometry and immunohistochemical evaluation of PR, ERα, AR, TRα, Kiss1 and Kiss1r. After 120 h of cabergoline or vitamin B6 treatment, PRL levels were reduced in the bitches, confirming the antiprolactinemic effect of these drugs. Furthermore, regardless of treatment, the animals exhibited uterine histomorphometry consistent with dioestrus. The PR showed strong immunostaining in all regions and an increase in scores was observed for this receptor in animals treated with vitamin B6 in deep glands. In contrast, ERα and Kiss1R receptors showed weak to no immunostaining in all uterine regions and no changes between groups. Regarding AR, most animals treated with vitamin B6 showed increased trends in the deep gland and myometrium marking scores. In contrast, in both vitamin B6 and cabergoline treatments, a reduction in TRα marking scores was observed compared to the control group. In addition, on the endometrial surface, a reduction was observed in the marked area of Kiss1 after administration of cabergoline when compared to the pseudopregnant control group. These findings shed valuable insight into the use of vitamin B6 as a drug with actions similar to cabergoline in reducing PRL and uterine modulation in bitches.

Rare Genetic Developmental Disabilities: Mabry Syndrome (MIM 239300) Index Cases and Glycophosphatidylinositol (GPI) Disorders.

The case report by Mabry et al. (1970) of a family with four children with elevated tissue non-specific alkaline phosphatase, seizures and profound developmental disability, became the basis for phenotyping children with the features that became known as Mabry syndrome. Aside from improvements in the services available to patients and families, however, the diagnosis and treatment of this, and many other developmental disabilities, did not change significantly until the advent of massively parallel sequencing. As more patients with features of the Mabry syndrome were identified, exome and genome sequencing were used to identify the glycophosphatidylinositol (GPI) biosynthesis disorders (GPIBDs) as a group of congenital disorders of glycosylation (CDG). Biallelic variants of the phosphatidylinositol glycan (PIG) biosynthesis, type V (PIGV) gene identified in Mabry syndrome became evidence of the first in a phenotypic series that is numbered HPMRS1-6 in the order of discovery. HPMRS1 [MIM: 239300] is the phenotype resulting from inheritance of biallelic PIGV variants. Similarly, HPMRS2 (MIM 614749), HPMRS5 (MIM 616025) and HPMRS6 (MIM 616809) result from disruption of the PIGO, PIGW and PIGY genes expressed in the endoplasmic reticulum. By contrast, HPMRS3 (MIM 614207) and HPMRS4 (MIM 615716) result from disruption of post attachment to proteins PGAP2 (HPMRS3) and PGAP3 (HPMRS4). The GPI biosynthesis disorders (GPIBDs) are currently numbered GPIBD1-21. Working with Dr. Mabry, in 2020, we were able to use improved laboratory diagnostics to complete the molecular diagnosis of patients he had originally described in 1970. We identified biallelic variants of the PGAP2 gene in the first reported HPMRS patients. We discuss the longevity of the Mabry syndrome index patients in the context of the utility of pyridoxine treatment of seizures and evidence for putative glycolipid storage in patients with HPMRS3. From the perspective of the laboratory innovations made that enabled the identification of the HPMRS phenotype in Dr. Mabry's patients, the need for treatment innovations that will benefit patients and families affected by developmental disabilities is clear.

Early pyridoxine administration rescues autism-like behavior in the BTBR T+tf/J autistic model

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment and repetitive, stereotyped behaviors. An imbalanced oxidative stress status and neuroinflammation are involved in ASD development. In this study, we investigated the effects of pyridoxine, a form of vitamin B6 with potent anti-oxidant and anti-inflammatory features, on autism-like behavior in BTBR T + ltpr3tf/J (BTBR) mice, a model of autism. Mice received pyridoxine from postnatal days 7 to 14. Behavioral tests were conducted on 8-week-old male mice, and the inflammatory status and oxidative stress levels were also assessed in the mouse hippocampus. Postnatal pyridoxine treatment significantly improved social deficits, stereotyped behaviors, and cognitive deficits in BTBR mice. In addition, pyridoxine treatment alleviated neuroinflammation in the hippocampus manifested by reduced Iba1+ microglia and inflammatory factors, such as interleukin-1β (IL-1β), IL-6, TNF-α, and NF-κB. Further, pyridoxine-treated BTBR mice had elevated Nrf2 and HO-1 in the hippocampus. Postnatal pyridoxine administration might improve autistic-like behaviors in BTBR mice via attenuating oxidative stress and neuroinflammation in the hippocampus.

Role of vitamin B12 and folic acid in treatment of Alzheimer's disease: a meta-analysis of randomized control trials.

Vitamin B12 and folic acid could reduce blood homocysteine levels, which was thought to slow down the progression of Alzheimer's disease (AD), but previous studies regarding the effect of vitamin B12 and folic acid in treatment of AD have not reached conclusive results. We searched PubMed and Embase until January 12, 2023. Only randomized control trials involving participants clearly diagnosed with AD and who received vitamin B12 and folic acid were enrolled. Five studies that met the criteria were selected for inclusion in the meta-analysis. Changes in cognitive function were measured based on either the Mini-Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Changes in daily life function and the level of blood homocysteine were also investigated. After a 6-month treatment, administration of vitamin B12 and folic acid improved the MMSE scores more than placebo did (SMD = 0.21, 95% CI = 0.01 to 0.32, p = 0.04) but did not significantly affect ADAS-Cog scores (SMD = 0.06, 95% CI = -0.22 to 0.33, p = 0.68) or measures of daily life function. Blood homocysteine levels were significantly decreased after vitamin B12 and folic acid treatment. Participants with AD who received 6 months of vitamin B12 and folic acid supplementation had better MMSE scores but had no difference in ADAS-Cog scores. Daily life function did not improve after treatment.

Biochemical and structural impact of two novel missense mutations in cystathionine β-synthase gene associated with homocystinuria.

Homocystinuria is a rare disease caused by mutations in the CBS gene that results in a deficiency of cystathionine β-synthase (CBS). CBS is an essential pyridoxal 5'-phosphate (PLP)-dependent enzyme in the transsulfuration pathway, responsible for combining serine with homocysteine to produce cystathionine, whose activity is enhanced by the allosteric regulator S-adenosylmethionine (SAM). CBS also plays a role in generating hydrogen sulfide (H2S), a gaseous signaling molecule with diverse regulatory functions within the vascular, nervous, and immune systems. In this study, we present the clinical and biochemical characterization of two novel CBS missense mutations that do not respond to pyridoxine treatment, namely c.689T > A (L230Q) and 215A > T (K72I), identified in a Chinese patient. We observed that the disease-associated K72I genetic variant had no apparent effects on the spectroscopic and catalytic properties of the full-length enzyme. In contrast, the L230Q variant expressed in Escherichia coli did not fully retain heme and when compared with the wild-type enzyme, it exhibited more significant impairments in both the canonical cystathionine-synthesis and the alternative H2S-producing reactions. This reduced activity is consistent with both in vitro and in silico evidence, which indicates that the L230Q mutation significantly decreases the overall protein's stability, which in turn, may represent the underlying cause of its pathogenicity.

Disrupted de novo pyrimidine biosynthesis impairs adult hippocampal neurogenesis and cognition in pyridoxine-dependent epilepsy.

Despite seizure control by early high-dose pyridoxine (vitamin B6) treatment, at least 75% of pyridoxine-dependent epilepsy (PDE) patients with ALDH7A1 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.

Case of Bovine’s Retained Placental (RP) Associated with a Subclinical Mastitis 3th Degree, Anémia and Parasitism

A 10-year-old black piebald cow is presented for persistence of the placenta, a sign of anemia plus a pitted coat and dejection. A transvaginal palpation plus a subclinical mastitis test of the 4 teats are performed showing an open cervix with 2 fingers plus a grade three subclinical mastitis of the right posterior teat. A hormonal medical intervention is carried out, allowing the expulsion of the placenta, the exploration of the cervix allowed the introduction of an intrauterine syringe. Antibiotic treatment, calcium therapy plus vitamin therapy based on vitamin A, vitamin E Selenium plus vitamin B12 plus antiparasitic treatment based on fenbendazole is implemented, allowing an improvement in the general condition and the absence of relapse during the 5 weeks of follow-up. According to the literature, this is the first published case of retained placenta/ parasitism/subclinical mastitis in a dairy cow in Algeria.

Neuropsychiatric disorders associated with recreational nitrous oxide use

Background Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. Purpose This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians’ awareness of this public health problem. Methods We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. Results There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted “V” sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. Conclusion Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

The effect of parenteral vitamin B12 on the growth rate of dairy calves over the summer and autumn on seven farms from the Central Plateau, New Zealand

ABSTRACTAimsTo investigate the effect of parenteral vitamin B12 supplementation on the growth rate of dairy heifer calves over the summer and autumn on seven farms from the Central Plateau of New Zealand, an area historically associated with low cobalt levels in grazing pasture.MethodsThis was a controlled clinical trial conducted on a convenience sample of seven farms with young female calves randomly assigned to three vitamin B12 treatment groups and followed through a grazing season. Two treatment groups received either monthly SC injections of a short-acting (SA) B12 formulation or 3-monthly injections of a long-acting (LA) B12 formulation and the third group received no treatment (NT). No additional parenteral vitamin B12 was given; however, all calves received additional cobalt (0.04–0.4 mg Co/kg liveweight) in the mineralised anthelmintic drenches given orally every month. Liveweight was recorded in December/January and at the end of the trial in May/June/July depending on farm. Pasture cobalt concentrations (mg/kg DM) were measured every month using 500-g herbage samples from 100-m transects in the area about to be grazed by the trial groups.ResultsThere was evidence for a difference in growth rate between groups with mean final weight of 228 (95% CI = 212–243) kg for the LA groups, 224 (95% CI = 209–239) kg for the SA groups and 226 (95% CI = 211–241) kg for the NT groups respectively, (global p-value = 0.014). Calves given SA vitamin B12 were 3.77 (95% CI = 0.71–6.82) kg lighter than calves given LA vitamin B12 (p = 0.011). There was no evidence for a change in pasture cobalt concentrations (p = 0.32).Conclusions and clinical relevanceThe results of this trial raise the question as to whether the routine use of vitamin B12 supplementation in young cattle from areas traditionally thought to be cobalt deficient is necessary, and further raise the possibility that vitamin B12 supplementation by repeated injection of SA products may negatively impact growth rates.

The Protective Effects of Pyridoxine on Linezolid-Induced Hematological Toxicity, Hepatotoxicity, and Oxidative Stress in Rats.

Linezolid is often used to treat antibacterial-resistant infections. Linezolid can cause side effects. To date, the effectiveness of the simultaneous administration of pyridoxine and linezolid is unclear. Here we investigate the protective effect of pyridoxine on linezolid-induced hematological toxicity, hepatotoxicity, and oxidative stress in rats. The 40 male pediatric Spraque-Dawley rats were separated into 4 groups: control, linezolid, pyridoxine, and linezolid-pyridoxine. A complete blood count, liver function test, and measurements of antioxidant enzyme activities for superoxide dismutase, glutathione peroxidase, catalase, and lipid peroxidation were performed in blood before treatment and 2 weeks after administration of the treatment. White blood cell and hemoglobin counts for the linezolid group decreased, and the alanine aminotransferase level in the linezolid group increased compared to their respective baseline values. Post-treatment white blood cell decreased in the linezolid and linezolid- pyridoxine groups compared to those in the control group (P < .001). Alanine aminotransferase levels increased in the linezolid and linezolid-pyridoxine groups compared to those in the control group (P < .001 and P < .05, respectively). The activity of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde levels increased in the linezolid group compared to the control group (P < .001, P < .05, P < .001, and P < .001, respectively). Linezolid plus pyridoxine treatment caused a significant decrease in malondialdehyde levels and superoxide dismutase, catalase, and glutathione peroxidase enzyme activities compared to the linezolid group (P < .001, P < .01, P < .001, and P < .01, respectively). Pyridoxine may be an effective adjuvant agent for the prevention of linezolid toxicity in rat models.

Structural and Functional Brain Changes Associated with Vitamin B12 Deficiency using Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

This review was conducted to assess the structural and functional brain changes associated with vitamin B12 deficiency in different age groups using MRI. PubMed, Embase, Medline, CINAHL, Scopus, Web of Science, and Google Scholar were searched for magnetic resonance imaging (MRI) studies that explored structural and functional brain changes associated with vitamin B12 deficiency in different age groups. The inclusion criteria were as follows: (1) the population consisted of people and not animals; (2) patients with known B12 deficiency; (3) English publications; (3) at least one of the following brain MRI techniques had been employed: VBM, DWI, DTI, fMRI, or rs-fMRI. However, case reports, systematic reviews and meta-analyses were excluded. Twelve articles met the inclusion criteria. The results of my review show a connection between vitamin B12 deficiency and abnormal structural and functional brain changes in several brain regions. These changes were observed in different age groups ranging from a mean age of seven years to a mean age in the 70s. The results also highlight the association between brain changes and cognitive decline among affected subjects. Improvements in damaged brain regions post-vitamin B12 treatment were also studied. Structural and functional brain damage was found to be associated with vitamin B12 deficiency in all age groups. Vitamin B12 treatment may lead to partial or complete structural and/or functional recovery, as well as a cognitive recovery.

Severe Microcytic Anemia Caused by Complex Hereditary Spherocytosis and X-Linked Sideroblastic Anemia with Mutations in SPTB and ALAS2 Genes

We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta (SPTB) and 5-aminolevulinic acid synthase (ALAS2) genes. The proband was a 16-year-old male with severe jaundice and microcytic hypochromic anemia since his childhood. He had more severe anemia requiring erythrocyte transfusion, and had no response to vitamin B6 treatment. Next-generation sequencing (NGS) revealed double heterozygous mutations, one in exon 19 (c.3936G > A:p.W1312X) of the SPTB gene and another in exon 2 (c.37A > G:p.K13E) of the ALAS2 gene, and confirmed again by Sanger sequencing. The mutation of ALAS2 (c.37A > G) is inherited from his asymptomatic heterozygous mother, causing amino acid p.K13E, and the mutation has not yet been reported. The mutation of SPTB (c.3936G > A) is a nonsense mutation, leading to a premature termination codon in exon 19, and the mutation in the SPTB gene is not found in any of his relatives, which indicates a de novo monoallelic mutation. Conclusions: The double heterozygous mutations in the SPTB and ALAS2 genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes.

The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study

BackgroundPyridoxine-dependent epilepsy (PDE) is a rare seizure disorder usually presenting with neonatal seizures. Most cases are caused by biallelic pathogenic ALDH7A1variants. While anti-seizure medications are ineffective, pyridoxine provides seizure control, and dietary interventions may be of benefit. As the natural history beyond adolescence is insufficiently explored, our study aimed to assess the spectrum of PDE at various ages in Norway. MethodsPatients were ascertained by contacting all Norwegian paediatric, neurological, and neurohabilitation departments and relevant professional societies. Medical records were collected and reviewed. ResultsWe identified 15 patients treated for PDE; 13 had ALDH7A1 variants (PDE-ALDH7A1), one had PNPO deficiency, and in one, aetiology remained obscure. Of those with PDE-ALDH7A1, 12 were alive at time of study; five were > 18 years old and six were < 4 years. Median age was 10 years (range 2 months–53 years). Estimated minimum prevalence was 6.3/million among children and 1.2/million among adults. Ten had seizure onset on the first day of life. Perinatal complications and neuroradiological abnormalities suggested additional seizure aetiologies in several patients. Pyridoxine had immediate effect in six, while six had delayed (>1 h) or uncertain effect. Median delay from first seizure to continuous treatment was 11 days (range 0–42). Nine experienced breakthrough seizures with intercurrent disease or due to pyridoxine discontinuation. Cognitive outcomes ranged from normal to severe intellectual disability. The condition appeared to remain stable in adult life. SignificanceWe found a much higher prevalence of PDE-ALDH7A1 in children relative to adults, suggesting previous underdiagnosis and early mortality. Perinatal complications are common and can delay diagnosis and initiation of pyridoxine treatment. Lifelong and continuous treatment with pyridoxine is imperative. Due to better diagnostics and survival, the number of adult patients is expected to rise.

Uticaj vitamina B6 na markere oksidativnog stresa, kardiometaboličke i histološke markere u uslovima monokrotalinom indukovane srčane slabosti kod Wistar albino pacova

Introduction/Aim: Heart failure (HF) induced by monocrotaline (MCT) is common in the pulmonary arterial vessels remodeling mechanisms with increased pulmonary resistance and oxidative stress markers. The purpose of this study was to validate the hypothesis that the treatment with vitamin B6 could affect HF by modulating cardiometabolic and oxidative stress biomarkers, and the structure of the rat heart. Material and Methods: Male Wistar albino rats were divided into 3 groups: blank solution-exposed control (C physiological saline 1ml/kg 28 days ip., n=8), B6 (vitamin B6 7mg/kg/day 28 days ip., n=8), and MCT+B6 (MCT 50mg/ kg once ip. plus vitamin B6 7mg/kg/day 28 days ip., n=8). Results: The four-week vitamin B6 treatment significantly affected certain biochemical parameters. The activity of key antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GPX) did not change, whereas the total glutathione (GSH) was significantly decreased in the MCT+B6 group. This was followed by a slightly decreased level of the total glutathionylation observed in the MCT+B6 group. The parameters of protein oxidative damage (reactive carbonyl derivates, thiol groups and nitrotyrosine) did not significantly change in the MCT+B6 group. An increasing trend in RV and LV wall thickness was observed in the MCT+B6 compared to the C group, as well as in Ki67 and PCNA positivity. Conclusion: The four-week treatment with vitamin B6 significantly affected certain biomarkers. The activity of SOD and nitrotyrosine content did not change, while GPX activity, total glutathione and total glutathionylation level were decreased in the MCT+B6 group. We observed an increase in RV and LV wall thickness in the MCT+B6 group compared to the C group, as well as in Ki67 and PCNA positivity.

Diagnosis and Treatment of Tuberculous Meningoencephalitis and Toxoplasma Encephalitis in Positive HIV Patient: Case Report

Background Tuberculous meningoencephalitis (TBME) and toxoplasma encephalitis (TE) are the most frequent cerebral opportunistic infections in positive HIV patients in developed countries. This study aims to determine a presumptive diagnosis of TBME and TE based only on clinical, CD4-count, and radiology features and to attend suitable early treatment for better patient outcomes. Case Description A 40-year-old presented to the emergency unit of dr. Mintohardjo Naval Hospital with decreased consciousness. History of positive HIV status, pulmonary tuberculosis for six months and anti-tubercular-treatment (ATT) drop-out. The GCS was E2M5V2, lung crackles, nuchal rigidity, positive Babinski reflex, and duplex hemiparesis. CD4-count: 4 cells/mm3. Multiple hypodense lesions, “finger-like-oedema”, featured on non-contrast head CT-scan. A lumbar puncture was not performed. Treatment of TBME included an ATT regimen, pyridoxine, cotrimoxazole, anti-oedema, and TE treatment included clindamycin and pyrimethamine. Based on the clinical and radiological diagnosis of TBME (nuchal rigidity, history of ATT drop-out, multiple hypodense lesions on CT-scan) and TE (altered mental status, duplex hemiparesis, CD4-count, “finger-like-oedema” projections on CT-scan), ATT and TE treatment were given for ten days. There were significant clinical improvements by GCS E4M6V3, negative nuchal rigidity after being treated early by ATT and TE treatment. Conclusions Presumptive Diagnosis of TBME and TE in HIV patients can be determined only based on clinical, CD4-count, and radiology examination. However, there are significant clinical improvements in giving ATT along with TE treatment immediately in positive HIV patients.

Possible association between vitamin B12 deficiency and restless legs syndrome

Restless Legs Syndrome (RLS) can be defined as a sleep disorder. However, whether changes in the serum vitamin B12 levels are involved in the pathophysiological mechanism of RLS remains unclear. Our study aimed to determine whether vitamin B12 levels are independently related to the occurrence of RLS. The serum vitamin B12 levels of 80 patients with RLS and 80 age- and gender-matched healthy controls (HC) were retrospectively analyzed. Serum vitamin B12 levels in the RLS group were significantly reduced, while the levels of creatinine, and homocysteine were higher (P<0.05). In addition, multivariate logistic regression revealed serum vitamin B12 to be independently associated with RLS (p<0.05; odds ratio=0.97; 95% confidence interval: 0.96-0.98). Pearson correlation analysis indicated that serum vitamin B12 level was negatively correlated with the International Restless Legs Scales (IRLS) score, and the 24-item Hamilton Depression Rating Scale (HAMD24) score (r=-0.025, P=0.023, r=-0.295, P=0.001). Patients with RLS had significant vitamin B12 deficiency compared to HC. Such deficiency significantly affects severity of symptoms and depression symptoms. In addition, decreased serum vitamin B12 levels are independently associated with the development of RLS, which illustrates the complex relationship between vitamin B12 and RLS. Prospective vitamin B12 treatment studies are needed to confirm this relationship and to evaluate the efficacy of vitamin B12 as a treatment for RLS patients.