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Lipids in Health and Disease Jul 2021LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is...
BACKGROUND
LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands.
METHODS
A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) Statement in Pubmed and SciELO. Articles which described subjects with LCAT deficiency syndromes and an assessment of the ethnic group to which the subject pertained, were included.
RESULTS
The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with fish eye disease identified later than familial LCAT deficiency (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD. In Latin America, 48 cases of LCAT deficiency have been published from six countries (Argentina (1 unclassified), Brazil (38 FLD), Chile (1 FLD), Columbia (1 FLD), Ecuador (1 FLD) and Mexico (4 FLD, 1 FED and 1 unclassified). Of the Mexican probands, one showed a novel LCAT mutation.
CONCLUSIONS
The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in fish eye disease compared to familial LCAT deficiency. In FLD, the emphasis should be in preventing both cardiovascular disease and the progression of renal disease, while in FED, cardiovascular risk management should be the priority. The LCAT mutations discussed in this article are the only ones reported in the Mexican- Amerindian population.
Topics: Ethnicity; Genetic Predisposition to Disease; Humans; Indians, North American; Lecithin Cholesterol Acyltransferase Deficiency; Mexico; Phosphatidylcholine-Sterol O-Acyltransferase; Racial Groups
PubMed: 34256778
DOI: 10.1186/s12944-021-01498-6 -
The Cochrane Database of Systematic... Feb 2015Phenylketonuria is an inherited metabolic disorder characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower... (Review)
Review
BACKGROUND
Phenylketonuria is an inherited metabolic disorder characterised by an absence or deficiency of the enzyme phenylalanine hydroxylase. The aim of treatment is to lower blood phenylalanine concentrations to the recommended therapeutic range to prevent developmental delay and support normal growth. Current treatment consists of a low-phenylalanine diet in combination with a protein substitute which is free from or low in phenylalanine. Guidance regarding the use, dosage, and distribution of dosage of the protein substitute over a 24-hour period is unclear, and there is variation in recommendations among treatment centres. This is an update of a Cochrane review first published in 2005, and previously updated in 2008.
OBJECTIVES
To assess the benefits and adverse effects of protein substitute, its dosage, and distribution of dose in children and adults with phenylketonuria who are adhering to a low-phenylalanine diet.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which consists of references identified from comprehensive electronic database searches and hand searches of relevant journals and abstract books of conference proceedings. We also contacted manufacturers of the phenylalanine-free and low-phenylalanine protein substitutes for any data from published and unpublished randomised controlled trials.Date of the most recent search of the Group's Inborn Errors of Metabolism Trials Register: 03 April 2014.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials comparing: any dose of protein substitute with no protein substitute; an alternative dosage; or the same dose, but given as frequent small doses throughout the day compared with the same total daily dose given as larger boluses less frequently.
DATA COLLECTION AND ANALYSIS
Both authors independently extracted data and assessed trial quality.
MAIN RESULTS
Three trials (69 participants) are included in this review. One trial investigated the use of protein substitute in 16 participants, while a further two trials investigated the dosage of protein substitute in a total of 53 participants. Due to issues with data presentation in each trial, described in full in the review, formal statistical analyses of the data were impossible. Investigators will be contacted for further information.
AUTHORS' CONCLUSIONS
No conclusions could be drawn about the short- or long-term use of protein substitute in phenylketonuria due to the lack of adequate or analysable trial data. Additional data and randomised controlled trials are needed to investigate the use of protein substitute in phenylketonuria. Until further evidence is available, current practice in the use of protein substitute should continue to be monitored with care.
Topics: Adult; Child; Dietary Proteins; Food, Formulated; Humans; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Randomized Controlled Trials as Topic
PubMed: 25723866
DOI: 10.1002/14651858.CD004731.pub4 -
Nutrients Sep 2022Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Observational studies reported inverse associations between serum total 25-hydroxyvitamin D (25(OH)D) concentrations and mortality. Evolving evidence indicated, however, that bioavailable or free 25(OH)D may be even better predictors of mortality. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence on associations of vitamin D-binding protein (VDBP), albumin-bound, bioavailable, and free 25(OH)D, with mortality.
METHODS
We systematically searched PubMed and Web of Science, up to 27 May 2022. Predictors of interest included serum or plasma concentrations of VDBP, albumin-bound, bioavailable, and free 25(OH)D. Assessed health outcomes were all-cause and cause-specific mortality. We included studies reporting associations between these biomarkers and mortality outcomes. We applied random-effects models for meta-analyses to summarize results from studies assessing the same vitamin D biomarkers and mortality outcomes.
RESULTS
We identified twelve eligible studies, including ten on VDBP, eight on bioavailable 25(OH)D, and eight on free 25(OH)D. No study reported on albumin-bound 25(OH)D and mortality. In meta-analyses, the highest levels of bioavailable and free 25(OH)D were associated with 37% (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.46, 0.87), and 29% (HR: 0.71, 95% CI: 0.53, 0.97) decrease in all-cause mortality, respectively, compared with the lowest levels. These estimates were similar to those for total 25(OH)D (HR: 0.67, 95% CI: 0.56, 0.80) observed in the same studies. Higher VDBP levels were associated with lower all-cause mortality in cancer patient cohorts. However, no such association was observed in general population cohorts.
CONCLUSIONS
Similar inverse associations of total, bioavailable, and free 25(OH)D with mortality suggest that bioavailable and free 25(OH)D do not provide incremental value in predicting mortality.
Topics: Albumins; Biomarkers; Humans; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein
PubMed: 36235547
DOI: 10.3390/nu14193894 -
Iranian Journal of Basic Medical... Sep 2017Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its... (Review)
Review
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its deficiency is implicated as a risk factor for multiple sclerosis. Here, we systematically reviewed the literature concerning the health benefits of riboflavin on MS. The literature recorded within four main databases, including relevant clinical trials, experimental, and case-control studies from 1976 to 2017 were considered. Both human and animal studies were included for review, with no restrictions on age, gender, or ethnicity. Experimental studies demonstrated that riboflavin deficiency triggers neurologic abnormalities related to peripheral neuropathies such as demyelinating neuropathy. Moreover, randomized controlled trials (RCT) and case-control studies in which MS patients received riboflavin supplementation or had higher dietary riboflavin intake showed improvements in neurological motor disability. Riboflavin is a cofactor of xanthine oxidase and its deficiency exacerbates low uric acid caused by high copper levels, leading to myelin degeneration. The vitamin additionally plays a significant role in the normal functioning of glutathione reductase (GR) as an antioxidant enzyme, and conditions of riboflavin deficiency lead to oxidative damage. Riboflavin promotes the gene and protein levels of brain-derived neurotrophic factor (BDNF) in the CNS of an animal model of MS, suggesting that BDNF mediates the beneficial effect of riboflavin on neurological motor disability. Research to date generally supports the role of riboflavin in MS outcomes. However, further observational and interventional studies on human populations are warranted to validate the effects of riboflavin.
PubMed: 29085589
DOI: 10.22038/IJBMS.2017.9257 -
Clinical Endocrinology May 2024Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in...
OBJECTIVE
Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia).
RESULTS
We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A.
CONCLUSIONS
We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.
Topics: Adolescent; Humans; Male; Female; Adrenal Hyperplasia, Congenital; Mutation; Phosphoproteins; Phenotype; Genotype; Disorder of Sex Development, 46,XY
PubMed: 38368602
DOI: 10.1111/cen.15032 -
Molecular Genetics and Metabolism 2022Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels.... (Review)
Review
BACKGROUND
Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels. It typically presents in early childhood with spasticity (predominately affecting the lower limbs), mobility impairment, seizures, developmental delay, and intellectual disability. This systematic review aims to identify and describe the published evidence outlining the epidemiology, diagnosis methods, measures of disease progression, clinical management, and outcomes for ARG1-D patients.
METHODS
A comprehensive literature search across multiple databases such as MEDLINE, Embase, and a review of clinical studies in ClinicalTrials.gov (with results reported) was carried out per PRISMA guidelines on 20 April 2020 with no date restriction. Pre-defined eligibility criteria were used to identify studies with data specific to patients with ARG1-D. Two independent reviewers screened records and extracted data from included studies. Quality was assessed using the modified Newcastle-Ottawa Scale for non-comparative studies.
RESULTS
Overall, 55 records reporting 40 completed studies and 3 ongoing studies were included. Ten studies reported the prevalence of ARG1-D in the general population, with a median of 1 in 1,000,000. Frequently reported diagnostic methods included genetic testing, plasma arginine levels, and red blood cell arginase activity. However, routine newborn screening is not universally available, and lack of disease awareness may prevent early diagnosis or lead to misdiagnosis, as the disease has overlapping symptomology with other diseases, such as cerebral palsy. Common manifestations reported at time of diagnosis and assessed for disease progression included spasticity (predominately affecting the lower limbs), mobility impairment, developmental delay, intellectual disability, and seizures. Severe dietary protein restriction, essential amino acid supplementation, and nitrogen scavenger administration were the most commonly reported treatments among patients with ARG1-D. Only a few studies reported meaningful clinical outcomes of these interventions on intellectual disability, motor function and adaptive behavior assessment, hospitalization, or death. The overall quality of included studies was assessed as good according to the Newcastle-Ottawa Scale.
CONCLUSIONS
Although ARG1-D is a rare disease, published evidence demonstrates a high burden of disease for patients. The current standard of care is ineffective at preventing disease progression. There remains a clear need for new treatment options as well as improved access to diagnostics and disease awareness to detect and initiate treatment before the onset of clinical manifestations to potentially enable more normal development, improve symptomatology, or prevent disease progression.
Topics: Infant, Newborn; Humans; Child, Preschool; Arginase; Intellectual Disability; Hyperargininemia; Seizures; Muscle Spasticity; Arginine; Amino Acids, Essential; Disease Progression; Nitrogen
PubMed: 36049366
DOI: 10.1016/j.ymgme.2022.08.005 -
Journal of Clinical Immunology Aug 2022Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3...
BACKGROUND
Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated with a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans.
OBJECTIVES
To explore interferon signaling in DNASE1L3 deficient patients. To depict the characteristic features of DNASE1L3 deficiencies in human.
METHODS
We identified, characterized, and analyzed five new patients carrying biallelic DNASE1L3 variations. Whole or targeted exome and/or Sanger sequencing was performed to detect pathogenic variations in five juvenile systemic erythematosus lupus (jSLE) patients. We measured interferon-stimulated gene (ISG) expression in all patients. We performed a systematic review of all published cases available from its first description in 2011 to March 24 2022.
RESULTS
We identified five new patients carrying biallelic DNASE1L3 pathogenic variations, including three previously unreported mutations. Contrary to canonical type I interferonopathies, we noticed a transient increase of ISGs in blood, which returned to normal with disease remission. Disease in one patient was characterized by lupus nephritis and skin lesions, while four others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented also with early-onset inflammatory bowel disease. Reviewing previous reports, we identified 35 additional patients with DNASE1L3 deficiency which was associated with a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Lung lesions were reported in 6/35 patients.
CONCLUSIONS
DNASE1L3 deficiencies are associated with a broad phenotype including frequently lupus nephritis and hypocomplementemic urticarial vasculitis with positive ANCA and rarely, alveolar hemorrhages and inflammatory bowel disease. This report shows that interferon production is transient contrary to anomalies of intracellular DNA sensing and signaling observed in Aicardi-Goutières syndrome or STING-associated vasculitis in infancy (SAVI).
Topics: Antibodies, Antineutrophil Cytoplasmic; Chromatin; DNA; Endodeoxyribonucleases; Humans; Inflammatory Bowel Diseases; Interferon Type I; Interferons; Lupus Erythematosus, Systemic; Lupus Nephritis; Phenotype; Vasculitis
PubMed: 35670985
DOI: 10.1007/s10875-022-01287-5 -
Health Promotion Perspectives 2020Diabetes is referred to a group of diseases characterized by high glucose levels in blood. It is caused by a deficiency in the production or function of insulin or... (Review)
Review
Diabetes is referred to a group of diseases characterized by high glucose levels in blood. It is caused by a deficiency in the production or function of insulin or both, which can occur because of different reasons, resulting in protein and lipid metabolic disorders. The aim of this study was to systematically review the prevalence and incidence of type 1 diabetes in the world. A systematic search of resources was conducted to investigate the prevalence and incidence of type 1 diabetes in the world. The databases of Medline (via PubMed and Ovid),ProQuest, Scopus, and Web of Science from January 1980 to September 2019 were searched to locate English articles. The located articles were screened in multiple levels of title, abstract,and full-text and final studies that met the inclusion criteria were retrieved and included in the study. From 1202 located articles, 193 studies were included in this systematic review. The results of meta-analysis showed that the incidence of type 1 diabetes was 15 per 100,000 people and the prevalence was 9.5% (95% CI: 0.07 to 0.12) in the world, which was statistically significant. According to the results, the incidence and prevalence of type 1 diabetes are increasing in the world. As a result, insulin will be difficult to access and afford, especially in underdeveloped and developing countries.
PubMed: 32296622
DOI: 10.34172/hpp.2020.18 -
Laboratory Investigation; a Journal of... Jul 2023The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho.... (Review)
Review
The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho. The purpose of this systematic review was to determine if there are biological and nutraceutical therapies that increase the expression of Klotho and can help prevent complications associated with chronic kidney disease. A systematic literature review was carried out through the consultation of PubMed, Scopus, and Web of Science. Records between the years 2012 and 2022 in Spanish and English were selected. Cross-sectional or prevalence and analytical studies were included that evaluated the effects of Klotho therapy. A total of 22 studies were identified after the critical reading of these selected studies: 3 investigated the association between Klotho and growth factors, 2 evaluated the relationship between the concentration of Klotho and the type of fibrosis, 3 focused on the relationship between vascular calcifications and vitamin D, 2 assessed the relationship between Klotho and bicarbonate, 2 investigated the relationship between proteinuria and Klotho, 1 demonstrated the applicability of synthetic antibodies as a support for Klotho deficiency, 1 investigated Klotho hypermethylation as a renal biomarker, 2 investigated the relationship between proteinuria and Klotho, 4 linked Klotho as an early marker of chronic kidney disease, and 1 investigated Klotho levels in patients with autosomal dominant polycystic kidney disease. In conclusion, no study has addressed the comparison of these therapies in the context of their use with nutraceutical agents that raise the expression of Klotho.
Topics: Humans; Cross-Sectional Studies; Glucuronidase; Kidney; Proteinuria; Renal Insufficiency, Chronic; Klotho Proteins
PubMed: 37207706
DOI: 10.1016/j.labinv.2023.100178 -
World Journal of Surgical Oncology Nov 2022Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is a need for meta-analyses with high statistical power to investigate and further explore their relationship.
METHODS
We used PubMed, Embase, the Cochrane Library, Scopus, MEDLINE, and the Web of Science to find studies on breast cancer and Slug. Overall survival (OS) and disease-free survival (DFS) were the study's primary endpoints. We pooled hazard ratios (HRs) and odds ratios (ORs) to assess the association between Slug protein expression and prognostic and clinicopathological parameters. This study was performed using STATA version 14.0 for data analysis. (Stata Corporation, TX, USA).
RESULTS
We conducted a literature search by searching six online databases. Ultimately, we obtained eight studies including 1458 patients through strict exclusion criteria. The results showed that increased Slug protein expression resulted in poorer OS (HR = 2.21; 95% CI = 1.47-3.33; P < 0.001) and DFS (HR = 2.03; 95% CI = 1.26-3.28; P = 0.004) in breast cancer patients. In addition, the results suggested that breast cancer patients with increased Slug protein expression had a higher TNM stage (I-II vs III-IV; OR = 0.42; 95% CI = 0.25-0.70; P = 0.001), a greater tendency to have axillary lymph node metastases (N+ vs N0; OR = 2.16; 95% CI = 1.31-3.56; P = 0.003) and were more prone to estrogen receptor deficiency (positive vs negative; OR = 0.67; 95% CI = 0.45-0.99; P = 0.042). However, Slug protein expression was not associated with age, histological grade, tumor size, progesterone receptor status, or human epidermal growth factor receptor 2 status in breast cancer patients.
CONCLUSION
This meta-analysis showed that elevated Slug protein expression may be related to poor outcomes in patients with breast cancer. Therefore, Slug is not only an indicator of patient survival but may also become a new target for breast cancer therapy.
Topics: Humans; Female; Prognosis; Breast Neoplasms; Disease-Free Survival; Lymphatic Metastasis; Receptors, Estrogen
PubMed: 36372891
DOI: 10.1186/s12957-022-02825-6