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Genes May 2024X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the...
X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the gene. Segregation analysis detected that the consultand's father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand's son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of transcripts with aberrant and wild-type splicing.
Topics: Humans; PHEX Phosphate Regulating Neutral Endopeptidase; Adult; Female; Familial Hypophosphatemic Rickets; Male; Pedigree; RNA Splice Sites; RNA Splicing; Phenotype; Genetic Diseases, X-Linked; Mutation
PubMed: 38927615
DOI: 10.3390/genes15060679 -
Biomedicines Jun 2024Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency.
BACKGROUND
Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency.
METHODS
Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women ( = 30) were recruited. Paired serum samples were analyzed for PFAAs ( = 13) using high-performance liquid chromatography-tandem mass spectrometry. Tandem mass spectrometry determined levels of 25(OH)D and the active 1,25(OH)D.
RESULTS
Women with and without PCOS did not differ in age, weight, insulin resistance, or systemic inflammation (C-reactive protein did not differ), but the free androgen index was increased. Four PFAAs were detected in all serum samples: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Serum PFOS was higher in PCOS versus controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, < 0.05). Linear regression modeling showed that elevated PFHxS had higher odds of a lower 25(OH)D (OR: 2.919, 95% CI 0.82-5.75, = 0.04). Vitamin D did not differ between cohorts and did not correlate with any PFAAs, either alone or when the groups were combined. When vitamin D was stratified into sufficiency (>20 ng/mL) and deficiency (<20 ng/mL), no correlation with any PFAAs was seen.
CONCLUSIONS
While the analyses and findings here are exploratory in light of relatively small recruitment numbers, when age, BMI, and insulin resistance are accounted for, the PFAAs do not appear to be related to 25(OH)D or the active 1,25(OH)D in this Caucasian population, nor do they appear to be associated with vitamin D deficiency, suggesting that future studies must account for these factors in the analysis.
PubMed: 38927462
DOI: 10.3390/biomedicines12061255 -
Scientific Reports Jun 2024Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease....
Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (β = - 0.14, P = 0.23; β = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D; Vitamin D Deficiency; Plaque, Atherosclerotic; Genome-Wide Association Study; Carotid Artery Diseases; Polymorphism, Single Nucleotide; Risk Factors; Genetic Predisposition to Disease; Female; Male; Carotid Arteries
PubMed: 38926411
DOI: 10.1038/s41598-024-64731-z -
Journal of Cachexia, Sarcopenia and... Jun 2024Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been...
BACKGROUND
Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been implicated in frailty, as it is essential for maintaining musculoskeletal functions. The relationship between dynamic changes in vitamin D levels and frailty over time has not been extensively studied.
METHODS
This study utilized data from the UK Biobank. Baseline and longitudinal changes in vitamin D levels were measured. Frailty status was assessed using both the frailty phenotype and frailty index approaches and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty phenotype at baseline (2006-2010) and the follow-up (2012-2013). Mixed effect model was performed to examine the association between vitamin D levels and frailty status. Using multistate transition models, we assessed the impact of increasing vitamin D levels on the probabilities of transitioning between robust, pre-frail, and frail states.
RESULTS
Based on the frailty phenotype, 287 926 individuals (64.8%) were identified as having various degrees of frailty (median age 58.00 [51.00, 64.00] years, 55.9% females). Using the frailty index approach, 250 566 individuals (56%) were found to have different levels of frailty (median age 59.00 [51.00, 64.00] years, 55.3% females). Baseline vitamin D levels were found to be significantly associated with frailty status (frailty phenotype: OR 0.78, 95% CI [0.76, 0.79], P < 0.001; frailty index: OR 0.80, 95% CI [0.78, 0.81], P < 0.001). Dynamic changes in vitamin D levels were also found to be associated with changes in frailty over time. Furthermore, increasing vitamin D levels were associated with a transition from frailty to a healthier status. A higher degree of vitamin D (estimated at 1 nmol/L) was associated with a lower risk of transitioning from robust to prefrail (HR 0.997, 95% CI [0.995, 0.999]) and from prefrail to frail (HR 0.992, 95% CI [0.988, 0.995]).
CONCLUSIONS
This study highlights the importance of vitamin D in the context of frailty. Low vitamin D levels are associated with increased frailty risk, while increasing vitamin D levels may contribute to improving frailty status. Recognizing the relationship between vitamin D levels and frailty can inform personalized management and early interventions for frail individuals. Further research is needed to explore the potential effects of vitamin D interventions on frailty and deepen our understanding of the biological connections between vitamin D and frailty.
PubMed: 38923848
DOI: 10.1002/jcsm.13525 -
Sports (Basel, Switzerland) May 2024Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D...
BACKGROUND
Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D in athletes. Indeed, vitamin D acts on the skeletal muscles and plays a fundamental role in numerous physiological processes involved in immune function. Many factors such as sun exposure, skin tone, body mass index and chronic illness affect vitamin D levels. The aim of the study is to evaluate vitamin D levels in professional football players in Italy and investigate the variations in vitamin D values in footballers who train at different latitudes.
METHODS
The study performed is a retrospective observational study analyzing 25-OH vitamin D values in professional football players of the Italian First Division (Serie A). Two teams during the competitive season were selected: team A (latitude of 41° N in southern Italy) and team B (latitude of 45° N in northern Italy). Three time periods were identified and were classified as follows: the first quarter (May, June, July, and August), the second quarter (September, October, November, and December) and the third quarter (January, February, March, and April). The purpose of this was to study the average values of vitamin D during the year corresponding to different levels of sunlight exposure. Each athlete was subjected to at least one sampling during the three quarters of the competitive season.
RESULTS
Both vitamin D insufficiency (10.1%) and overt deficiency (1.93%) were found in Italian Serie A players. Insufficient vitamin D values are between 20 ng/mL and 29 ng/mL and overt deficiency values <20 ng/mL. At the same time, the data demonstrated a significant variation in vitamin D values depending on the period of the competitive season and the latitude of the cities of the two teams. In detail, there was no significant difference in the first quarter, while there was a significant increase in vitamin D values in team B in the second and third quarter, at < 0.01 and < 0.05, respectively.
CONCLUSIONS
Latitude and seasons have a significant impact on vitamin D levels. Therefore, it is essential to measure vitamin D in professional football players, especially during the spring and winter months, so as to monitor changes in levels in relation to the season and latitude and evaluate any supplements. Further studies should be performed to evaluate the relationship between vitamin D deficiency and football players' athletic performance.
PubMed: 38921847
DOI: 10.3390/sports12060153 -
Dentistry Journal May 2024This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic... (Review)
Review
This review's objective is to examine the findings from various studies on oral signs and symptoms related to vitamin deficiency. In October 2023, two electronic databases (Scopus and PubMed) were searched for published scientific articles following PRISMA principles. Articles eligible for inclusion in this review had to be published in English between 2017 and 2023, be original studies, and involve human subjects. Fifteen studies were included in this review: three examining oral symptoms of vitamin B12 deficiency; one assessing vitamin B complex and vitamin E for recurrent oral ulcers; one investigating serum vitamin D levels in recurrent aphthous stomatitis patients; three exploring hypovitaminosis effects on dental caries; two measuring blood serum vitamin D levels; one evaluating vitamin B12 hypovitaminosis; three investigating hypovitaminosis as indicative of gingival disease; one focusing on vitamin deficiencies and enamel developmental abnormalities; one assessing vitamin deficiencies in oral cancer patients; one examining vitamin K as an oral anticoagulant and its role in perioperative hemorrhage; and one evaluating vitamin effects on burning mouth syndrome. Despite some limitations, evidence suggests a correlation between vitamin deficiencies and oral symptoms. This systematic review was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) database (202430039).
PubMed: 38920853
DOI: 10.3390/dj12060152 -
International Journal of Neonatal... Jun 2024Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of...
Vitamin B12 (B12) deficiency (B12D) can have detrimental effects on early growth and development. The Austrian newborn screening (NBS) program targets inborn errors of cobalamin metabolism and also detects B12D. Of 59 included neonates with B12D suspected by NBS, B12D was not further investigated in 16 (27%) retrospectively identified cases, not confirmed in 28 (48%), and confirmed in 15 (25%) cases. NBS and recall biomarkers were recorded. Age at sampling of the dried blood spots for NBS and the 1st-tier methionine/phenylalanine ratio were the strongest parameters to predict B12D (67.4% correct allocations). No differences between cases with confirmed, unconfirmed, or unknown B12D or differences to norms were observed for growth and psychomotor development (Vineland III scales, phone interviews with parents of children between months 10 and 14 of life). B12 intake was below recommendations in most mothers. NBS can detect reduced intracellular B12 activity. No advantage of NBS detection and treatment regarding infant cognitive development or growth could be proven. Since conspicuous NBS findings cannot be ignored, and to prevent exposing newborns to invasive diagnostics, assessment of maternal B12 status during pregnancy seems advisable.
PubMed: 38920847
DOI: 10.3390/ijns10020040 -
Frontiers in Nutrition 2024The growing prevalence of vegetarianism determines the need for comprehensive study of the impact of these diets on health and particularly on bone metabolism. We...
INTRODUCTION
The growing prevalence of vegetarianism determines the need for comprehensive study of the impact of these diets on health and particularly on bone metabolism. We hypothesized that significant dietary differences between vegans, lacto-ovo-vegetarians, and omnivores also cause significant differences in their nutrient status, which may affect bone health.
METHODS
The study assessed dual-energy X-ray absorptiometry parameters in lumbar spine and femoral neck, average nutrient intake, serum nutrient concentrations, serum PTH levels, and urinary pH among 46 vegans, 38 lacto-ovo-vegetarians, and 44 omnivores.
RESULTS
There were no differences in bone mineral density (BMD) between the groups. However, the parathyroid hormone (PTH) levels were still higher in vegans compared to omnivores, despite the same prevalence of hyperparathyroidism in all groups. These findings may probably be explained by the fact that each group had its own "strengths and weaknesses." Thus, vegans and, to a lesser extent, lacto-ovo-vegetarians consumed much more potassium, magnesium, copper, manganese, and vitamins B, B, and C. At the same time, the diet of omnivores contained more protein and vitamins D and B. All the subjects consumed less vitamin D than recommended. More than half of vegans and omnivores had insufficiency or even deficiency of vitamin D in the blood. Low serum concentrations of manganese with its quite adequate intake are also noteworthy: its deficiency was observed in 57% of vegans, 79% of lacto-ovo-vegetarians, and 63% of omnivores.
DISCUSSION
Currently, it is no longer possible to conclude that lacto-ovo-vegetarians have lower BMD than omnivores, as our research supported. Vegans in our study also did not demonstrate lower BMD values, only higher PTH blood concentrations, compared to omnivores, however, a large number of studies, including recent, show the opposite view. In this regard, further large-scale research is required. Vegans and lacto-ovo-vegetarians now have a variety of foods fortified with vitamins D and B, as well as calcium. There is also a great diversity of ethically sourced dietary supplements. The found low concentrations of manganese require further investigation.
PubMed: 38919395
DOI: 10.3389/fnut.2024.1390773 -
Cureus May 2024Vitamin B12 plays an important role in DNA synthesis, hematopoiesis, and neuronal mechanisms, and its deficiency can be associated with insufficient intake or poor...
Vitamin B12 plays an important role in DNA synthesis, hematopoiesis, and neuronal mechanisms, and its deficiency can be associated with insufficient intake or poor absorption and autoimmune and genetic diseases. Although rare, excessive, and chronic alcohol consumption may also justify a deficiency in this vitamin. We present a case of a 17-year-old Iraqi adolescent refugee in Portugal with a deficiency of vitamin B12 due to excessive and chronic alcohol consumption. Although intramuscular (IM) supplementation with cyanocobalamin is the most used, it was decided to initiate oral supplementation. After four months, vitamin B12 levels were replenished. With this clinical case, we aim to raise awareness of the cause of cyanocobalamin deficiency, which although rare in pediatric age should be considered in adolescents, given the possibility of risky behaviors in this age group. Additionally, given the therapeutic options, we have found that oral administration of vitamin B12 has been effective, as reported in the literature.
PubMed: 38919202
DOI: 10.7759/cureus.61123 -
International Journal of Surgery Case... Jun 2024Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia,...
INTRODUCTION AND IMPORTANCE
Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia, burning sensations, and pruritus. These oral signs can serve as early indicators of systemic conditions such pernicious anemia.
CASE PRESENTATION
A 67 year old northern African female presented at the oral surgery service with complaints of a sore mouth and difficulty eating certain types of food. Her medical history revealed hypothyroidism and no history of gastrectomy. She was diagnosed with pernicious anemia in 2014 and is under hydroxocobalamin injection 5000μg/month since then. Dental history indicated extraction of all teeth, and in 2014, the patient was diagnosed with oral lichen planus. There were no contributory oral habits. Intraoral examination revealed a band like erythematous lesion on the palate with two superficial ulcerations, diagnosed as related to her pernicious anemia. The patient was prescribed a mouthwash containing sodium bicarbonate and corticosteroid to reduce inflammation and alleviate pain. A low level laser therapy was also considered to reduce the burning sensations.
CLINICAL DISCUSSION
Pernicious anemia (PA) is an autoimmune disease characterized by the gradual atrophy of the gastric mucosa, predominantly affecting the body and fundus of the stomach, leading to vitamin B12 deficiency. Its insidious onset often masks its presence. Patients have no anemic symptoms. However, they can present with oral manifestations related to vitamin B12 deficiency. Those oral signs can precede hematological symptoms helping in early diagnosis of PA.
CONCLUSION
Dentists and other oral health care providers must be aware of this condition and its oral manifestations. Investigating vitamin B12 levels should be considered in patients presenting with oral ulcers, oral erythema or burning sensations without an apparent origin.
PubMed: 38917702
DOI: 10.1016/j.ijscr.2024.109931