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International Journal of Neonatal... Jun 2024Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder and the most common type of muscular dystrophy in children. As newborn screening (NBS) for DMD...
Age-Related Blood Levels of Creatine Kinase-MM in Newborns and Patients with Duchenne Muscular Dystrophy: Considerations for the Development of Newborn Screening Algorithms.
Duchenne muscular dystrophy (DMD) is an X-linked progressive disorder and the most common type of muscular dystrophy in children. As newborn screening (NBS) for DMD undergoes evaluation for the Recommended Uniform Screening Panel and is already mandated in multiple states, refining NBS algorithms is of utmost importance. NBS for DMD involves measuring creatine kinase-MM (CK-MM) concentration-a biomarker of muscle damage-in dried blood spots. The current test is FDA-approved for samples obtained less than 72 h after birth. Separate reference ranges are needed for samples collected later than 72 h after birth. In this study, we investigated the relationship between age and CK-MM in presumed healthy newborns to inform NBS algorithm designs. In patients with DMD, CK-MM is persistently elevated in childhood and adolescence, while it may be transiently elevated for other reasons in healthy newborns. CK-MM decrease over time was demonstrated by a population sample of 20,306 presumed healthy newborns tested between 0 and 60 days of life and repeat testing of 53 newborns on two separate days. In the population sample, CK-MM concentration was highest in the second 12 h period of life (median = 318 ng/mL) when only 57.6% of newborns tested below 360 ng/mL, the lowest previously published cutoff. By 72 h of age, median CK-MM concentration was 97 ng/mL, and 96.0% of infants had concentrations below 360 ng/mL. Between 72 h and 60 days, median CK-MM concentration ranged from 32 to 37 ng/mL. Establishing age-related cutoffs is crucial for optimizing the sensitivity and specificity of NBS for DMD.
PubMed: 38920848
DOI: 10.3390/ijns10020041 -
American Journal of Human Genetics Jun 2024The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A...
The neurodevelopmental disorders Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS) both arise from genomic alterations within human chromosome 15q11-q13. A deletion of the SNORD116 cluster, encoding small nucleolar RNAs, or frameshift mutations within MAGEL2 result in closely related phenotypes in individuals with PWS or SYS, respectively. By investigation of their subcellular localization, we observed that in contrast to a predominant cytoplasmic localization of wild-type (WT) MAGEL2, a truncated MAGEL2 mutant was evenly distributed between the cytoplasm and the nucleus. To elucidate regulatory pathways that may underlie both diseases, we identified protein interaction partners for WT or mutant MAGEL2, in particular the survival motor neuron protein (SMN), involved in spinal muscular atrophy, and the fragile-X-messenger ribonucleoprotein (FMRP), involved in autism spectrum disorders. The interactome of the non-coding RNA SNORD116 was also investigated by RNA-CoIP. We show that WT and truncated MAGEL2 were both involved in RNA metabolism, while regulation of transcription was mainly observed for WT MAGEL2. Hence, we investigated the influence of MAGEL2 mutations on the expression of genes from the PWS locus, including the SNORD116 cluster. Thereby, we provide evidence for MAGEL2 mutants decreasing the expression of SNORD116, SNORD115, and SNORD109A, as well as protein-coding genes MKRN3 and SNRPN, thus bridging the gap between PWS and SYS.
PubMed: 38908375
DOI: 10.1016/j.ajhg.2024.05.023 -
Orphanet Journal of Rare Diseases Jun 2024Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in...
BACKGROUND
Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis.
RESULTS
We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles.
CONCLUSIONS
The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS.
Topics: Humans; Prader-Willi Syndrome; Female; Male; Genotype; Phenotype; Brazil; Child, Preschool; Child; Adolescent; Adult; Uniparental Disomy; Chromosomes, Human, Pair 15; Infant; Young Adult
PubMed: 38902749
DOI: 10.1186/s13023-024-03157-2 -
Pediatrics and Neonatology Jun 2024
PubMed: 38902162
DOI: 10.1016/j.pedneo.2024.06.002 -
World Journal of Clinical Cases Jun 2024As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many...
BACKGROUND
As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes.
CASE SUMMARY
Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved.
CONCLUSION
Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.
PubMed: 38899290
DOI: 10.12998/wjcc.v12.i16.2813 -
Trials Jun 2024Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability...
Transcutaneous auricular vagus nerve stimulation to acutely reduce emotional vulnerability and improve emotional regulation in borderline personality disorder (tVNS-BPD): study protocol for a randomized, single-blind, sham-controlled trial.
BACKGROUND
Borderline personality disorder (BPD) is considered a disorder of emotion regulation resulting from the expression of a biologically determined emotional vulnerability (that is, heightened sensitivity to emotion, increased emotional intensity/reactivity, and a slow return to emotional baseline) combined with exposure to invalidating environments. Vagal tone has been associated with activity in cortical regions involved in emotion regulation and a lower resting state of vagal tone has been observed in BPD patients relative to healthy controls. Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to reduce temper outbursts in adults with Prader-Willi Syndrome, to enhance recognition of emotions in healthy students, and to improve depressive and anxiety symptoms. Furthermore, a single session of taVNS has been shown to acutely alter the recognition of facial expressions of negative valence in adolescents with MDD and increase emotion recognition in controls. However, the effect of taVNS on emotional vulnerability and regulation in individuals diagnosed with BPD has not been investigated. Our aims are to determine if taVNS is effective in acutely reducing emotional vulnerability and improve emotional regulation in BPD patients.
METHODS
Forty-two patients will be randomized to a single session of taVNS or sham-taVNS while going through an affect induction procedure. It will consist of the presentation of one neutral and three negative affect-evoking 4-min-long videos in sequence, each of which is followed by a 4-min post-induction period during which participants will rate the quality and intensity of their current self-reported emotions (post-induction ratings) and the perceived effectiveness in managing their emotions during the video presentation. The rating of the current self-reported emotions will be repeated after every post-induction period (recovery ratings). Mixed models with individuals as random effect will be used to investigate the ratings at each stage of the study, taking into account the repeated measures of the same individuals at baseline, pre-induction, post-induction, and recovery.
DISCUSSION
The study has potential to yield new insights into the role of vagal tone in emotion dysregulation in BPD and offer preliminary data on the effectiveness of taVNS as a possible non-invasive brain stimulation to treat a core symptom of BPD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05892900. Retrospectively registered on Jun 07, 2023.
Topics: Humans; Borderline Personality Disorder; Vagus Nerve Stimulation; Emotional Regulation; Single-Blind Method; Adult; Randomized Controlled Trials as Topic; Emotions; Transcutaneous Electric Nerve Stimulation; Young Adult; Female; Treatment Outcome; Male; Adolescent; Time Factors; Vagus Nerve; Middle Aged
PubMed: 38898522
DOI: 10.1186/s13063-024-08230-6 -
Journal of Clinical Medicine Jun 2024: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home...
: Strict regimens of restricted caloric intake and daily physical exercise are life-saving in Prader-Willi syndrome (PWS) but are extremely challenging in home environments. PWS-specialized hostels (SH) succeed in preventing morbid obesity and in coping with behavioral disorders; however, effects of restricted living environments on quality of life (QOL) have not been described. Evidence on QOL is critical for clinicians involved in placement decisions. : We examined the impact of living in SH versus at home or in non-specialized hostels (H and NSH) on QOL, behavior, and health parameters. All 58 adults (26 males) followed-up in the National Multidisciplinary Clinic for PWS were included: 33 resided in SH, 18 lived at home, and 7 lived in NSH. Questionnaires were administered to primary caregivers to measure QOL, and data were obtained from the medical records. : The H and NSH group were compared with those for adults in SH. Despite strict diet and exercise regimens, QOL was similar for both groups. Eight-year follow-up showed that food-seeking behavior decreased in SH but increased in H and NSH. BMI, cholesterol, and triglyceride levels were lower in SH. : Our results suggest that living in SH is associated with benefits for physical health and behavior without negatively affecting QOL.
PubMed: 38893034
DOI: 10.3390/jcm13113323 -
The Journal of Biological Chemistry Jun 2024Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases...
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PD) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PD variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PD variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PD variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.
PubMed: 38876306
DOI: 10.1016/j.jbc.2024.107460 -
Missouri Medicine 2024Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental disorder with multisystem impact and a unique behavior profile that evolves over the life span.... (Review)
Review
Prader-Willi syndrome (PWS) is a complex genetic neurodevelopmental disorder with multisystem impact and a unique behavior profile that evolves over the life span. Beyond the primary care needs of all children and adults, the unique medical concerns and management needs of those with PWS are best served in a multidisciplinary academic center. Our PWS center has provided care for individuals with PWS and their families since 1981. Our growth hormone studies contributed to growth hormone supplementation becoming standard of care in this country. Here, in collaboration with the primary care provider, early childhood intervention programs, schools and local parent organizations, solid, patient-centered care for affected individuals and their families can be provided across the life-span. The purpose of this article is to provide a brief overview of PWS and the attendant medical and behavior management challenges attendant to the disorder.
Topics: Prader-Willi Syndrome; Humans; Child; Human Growth Hormone
PubMed: 38854617
DOI: No ID Found -
Translational Pediatrics May 2024Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal...
BACKGROUND
Prader-Willi syndrome (PWS) is a multisystem genetic disorder caused by chromosomal imprinting gene defects, with approximately 70% of cases resulting from paternal deletion of the chromosomal region 15. The main clinical features include severe infantile hypotonia, early-onset childhood obesity, hyperphagia, and underdeveloped external genitalia. As individuals with PWS age, they may exhibit irritability, social dysfunction, impaired gonadal development, and metabolic syndrome. Previous literature places the prevalence of type 2 diabetes mellitus (T2DM) in PWS at approximately 7-24%. Oxytocin is a neuropeptide secreted by the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus and regulates energy metabolism, which is involved in PWS. Due to age limitations, very few patients progress to diabetic nephropathy during childhood, and reports of typical diabetic nephropathy in PWS during childhood are extremely rare. Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist which can be used in the treatment of T2DM.
CASE DESCRIPTION
This article reports a case of a child with PWS complicated by stage III diabetic nephropathy, providing a retrospective analysis of the diagnosis and treatment process, as well as a review of domestic and international literature, to enhance understanding of this condition. And this article provides a treatment idea for PWS patients with diabetic nephropathy.
CONCLUSIONS
It is very important to enhance understanding of PWS. And we offer new diagnostic and possible therapeutic approaches for pediatric patients with diabetic nephropathy.
PubMed: 38840685
DOI: 10.21037/tp-23-518