Group Of Diseases Research Articles

Comparison of Longitudinal Outcomes in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis.

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder in childhood than CF, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD: pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD) are associated with more severe disease. To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). Children with PCD enrolled in a prospective, multicenter, observational study were matched with CF patients from the CF Foundation Patient Registry by birth cohort, age, sex, race/ethnicity and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD versus all other defects and CF-minimal versus residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean FEV1 % predicted compared to CF (e.g., at age 10, -5.4 % predicted lower (95% CI: -7.7, -3.1)). Compared to the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar BMI; estimated mean FEV1 % predicted was significantly lower by age 10 (mean difference -10.6% (95% CI: -14.7, -6.4), increasing to -15.7% (95% CI: -20.3, -11.2) at age 14. The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared to children with PCD (67% vs 27%, p<0.001); there was no difference in prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other. In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.

Benign Tumors and Tumor-Like Conditions of Ampulla and Small Intestine: The PathologyOutlines.com Review.

Small intestine and ampulla can be involved in a heterogeneous group of benign tumors and tumor-like diseases, potentially mimicking malignant neoplasms. In-depth knowledge of them is critical for practicing pathologists since they represent potential pitfalls in routine diagnostic activity. Such conditions include the following: (1) Brunner gland lesions, including Brunner gland hyperplasia and hamartoma; (2) polyps, such as adenoma, hyperplastic, hamartomatous, and inflammatory; (3) mesenchymal proliferations encompassing inflammatory fibroid polyp, inflammatory myofibroblastic tumor, leiomyomas, lipomas, and lipomatosis of the ileocecal valve; (4) fibrosis-associated diseases, such as idiopathic retroperitoneal fibrosis, reactive nodular fibrous pseudotumor, and sclerosing peritonitis; (5) disorders of lymphatic vessels, including lymphangiectasia and lymphangiomas; and (6) other rare conditions/miscellanea, such as enteritis cystica profunda, intussusception, ischemia, and pneumatosis cystoides intestinalis. This review, inspired by the content of the PathologyOutlines website (https://www.pathologyoutlines.com), aims to provide a reference point in this complex scenario, summarizing the essential histopathological features of all these entities for better addressing routine practice and differential diagnoses.

A RETREG1 variant is associated with hereditary sensory and autonomic neuropathy with acral self-mutilation in purebred German Spitz.

Hereditary sensory and autonomic neuropathies (HSAN) represent a group of genetic diseases affecting the peripheral nervous system. In humans, at least 16 loci have been associated with the disorder but do not explain the disease origin of all patients. In dogs, similar conditions have been documented for decades in various breeds with a severe impact on life quality and are often referred to as acral mutilation syndrome (AMS). Causal variants in three genes have been identified to date, suggesting larger genetic heterogeneity in the dog population. Our aim was to explain the genetic etiology of an early-onset HSAN/AMS in a purebred German Spitz. The affected dog showed progressive loss of pain sensation in the distal extremities, which led to intense licking, biting, and self-mutilation of digits and paw pads. Whole-genome sequencing identified a single candidate causal variant on chromosome 4 in the RETREG1 gene (c.656C>T, p.Pro219Leu). This missense variant was previously recognized as deleterious in a mixed breed dog family with similar clinical signs. Haplotype analyses and targeted genotyping revealed a likely German Spitz ancestry of these mixed breed dogs. Further screening of an extensive cohort of ~900 000 dogs of various breeds hinted at the variant allele origin in the German Spitz breed. Disruption of RETREG1 inhibits endoplasmic reticulum turnover and leads to neuron degeneration. Our findings provide evidence that this variant underlies the recessive form of HSAN/AMS in the German Spitz and support the use of whole-genome sequencing-based veterinary precision medicine for early diagnosis and prevention via a genetic test.

Clinical Outcomes of Concomitant Coronary Artery Bypass Grafting During Ventricular Septal Myectomy.

The clinical characteristics and survival outcomes of patients who underwent concomitant coronary artery bypass grafting during septal myectomy have not been well studied. We reviewed patients who underwent both septal myectomy and coronary artery bypass grafting from 2009 to 2020. Causes of concomitant grafting and their impact on survival were analyzed. The median follow-up period was 5.1 years. A total of 320 patients underwent both grafting and myectomy. Of these, 69.7% and 28.1% underwent grafting attributed to atherosclerotic coronary artery disease and myocardial bridging, respectively. Patients who underwent grafting for coronary artery disease tended to be older, had a longer bypass time, and required more grafts compared with patients undergoing procedures because of myocardial bridging (all P<0.05). Postoperatively, the left ventricular outflow gradient significantly decreased from 85.4 mm Hg to 12.8 mm Hg (P<0.001) without perioperative death. The cumulative survival rates were 96.2% and 97.6% at 5 years in the coronary artery disease and myocardial bridging groups, respectively, and they were comparable to that of general myectomy cohort (hazard ratio [HR], 1.06 [95% CI, 0.47-2.36], P=0.895 and HR 0.75 [95% CI, 0.23-2.46], P=0.636, respectively). Sudden death accounted for 45.5% (5 of 11) of postoperative mortality. Analysis of composite end point events showed decreased morbidity with at least one arterial graft in the overall cohort (HR, 0.47 [95% CI, 0.23-0.94], P=0.034). Concomitant grafting in septal myectomy was found to be a safe procedure. Patients who underwent such surgery experienced favorable postoperative outcomes comparable to those who underwent septal myectomy alone, with a 5-year survival rate of >95% and improved functional class of >90%.

MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma.

Group 3 medulloblastoma (MBGRP3) represents around 25% of medulloblastomas and is strongly associated with c-MYC (MYC) amplification, which confers significantly worse patient survival. Although elevated MYC expression is a significant molecular feature in MBGRP3, direct targeting of MYC remains elusive, and alternative strategies are needed. The metabolic landscape of MYC-driven MBGRP3 is largely unexplored and may offer novel opportunities for therapies. To study MYC-induced metabolic alterations in MBGRP3, we depleted MYC in isogenic cell-based model systems, followed by 1H high-resolution magic-angle spectroscopy (HRMAS) and stable isotope-resolved metabolomics, to assess changes in intracellular metabolites and pathway dynamics. Steady-state metabolic profiling revealed consistent MYC-dependent alterations in metabolites involved in one-carbon metabolism such as glycine. 13C-glucose tracing further revealed a reduction in glucose-derived serine and glycine (de novo synthesis) following MYC knockdown, which coincided with lower expression and activity of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in this pathway. Furthermore, MYC-overexpressing MBGRP3 cells were more vulnerable to pharmacological inhibition of PHGDH compared to those with low expression. Using in vivo tumor-bearing genetically engineered and xenograft mouse models, pharmacological inhibition of PHGDH increased survival, implicating the de novo serine/glycine synthesis pathway as a pro-survival mechanism sustaining tumor progression. Critically, in primary human medulloblastomas, increased PHGDH expression correlated strongly with both MYC amplification and poorer clinical outcomes. Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.

Risk, Attributable Fraction and Attributable Number of Cause-Specific Heat-Related Emergency Hospital Admissions in Switzerland.

We assessed the relationship between heat and emergency hospital admissions (EHAs) in Switzerland using clinically relevant metrics. Applying distributed lag non-linear models, we investigated temperature-admission associations between May and September 1998-2019 for various disease groups, by age class and gender. We estimated the relative risk (RR) for moderate (29°C) and extreme (34°C) daily maximum temperatures relative to disease-specific optimum temperature, and calculated attributable fractions (AFs) for hot days and the following week. We also calculated the total number of heat-related EHAs. We attributed 31,387 (95% confidence interval: 21,567-40,408) EHAs to above-optimal temperatures, 1.1% (0.7%-1.4%) of the total. Extreme temperatures increased the EHA risk for mental, infectious and neurological diseases. We observed particularly high AFs due to extreme heat for dehydration (85.9%, 95% CI: 82.4%-88.8%) and acute kidney injury (AKI, 56.1%, 95% CI: 45.3%-64.7%). While EHA risk generally increased with age, we also found high RRs for infectious diseases in children (0-15years) and AKI in young adults (15-64years). Hot weather increases the EHA risk in Switzerland. Therefore a comprehensive clinical and public health response is needed.

Light Chain (AL) Amyloidosis for Nephrologists - Treatment Standard.

Amyloidosis is a group of complex diseases caused by the misfolding and aggregation of proteins into amyloid fibrils. AL amyloidosis is one of the most prevalent forms of amyloidosis, characterized by the gradual proliferation of light chains from plasma cell clones. A growing body of evidence has contributed to our understanding of its pathogenesis, presentation, and clinical course. Increased recognition of its clinical sequelae has increased the prevalence of AL amyloidosis. Renal involvement, seen in up to 70% of cases, is particularly challenging due to its impact on quality of life and access to treatment options. Thus, early recognition of its unique sequelae, appropriate staging, and a comprehensive understanding of treatment options balanced by their organ toxicities are crucial to managing this disease. We review the current treatment standards and discuss novel developments in the pathophysiology, diagnosis, outcome prediction, and management of AL amyloidosis for the Nephrologist.

A Rare Case of Early Infantile Neuronal Ceroid Lipofuscinosis: Clinical and Diagnostic Insights

The Aim of the Study: The aim of this work is to show the different specific clinical and paraclinical aspects of ceroid lipofuscinosis in its early infantile form named Santavuori-Haltia disease through a new case.Given its rarety especially in consanguineous populations for better understanding the clinical presentation,progression and management of the disease. Introduction: The neuronal ceroid lipofuscinoses are a group of genetic brain diseases with an autosomal recessive manner characterized by the accumulation of an autofluorescent material in multiple tissues of patients. Clinically, they are progressive decline of mental and motor capacities, epilepsy and visual loss through retinal degeneration . In this work we report the early infantile neuronal ceroid lipofuscinosis or Santavuori-Haltia disease. Report Case: This is a 12-month-old infant from consanguineous parents who has presented with flexion spasms with eyelid clonia since the age of 1 month. The examination found microcephaly, and the neurological examination showed horizontal nystagmus with the absence of ocular pursuit and the presence of a pyramidal and extrapyramidal syndrome. Brain MRI shows delayed myelination. Skin biopsy confirms diagnosis. The Arg122Trp genetic mutation found is the most common one in this disease. Conclusion: Santaviori-Haltia disease is a rare and serious disease, the prognosis is severe, it must be mentioned in the face of psychomotor regression and a picture of encephalopathy. Confirmation of the diagnosis is based on histological and molecular biology data.

Potential In Vitro Antimelanoma Effect of the Essential Oil from Croton grewioides Baill.

Cancer is a group of diseases characterized by uncontrolled cell growth, invasive capacity, and metastatic potential. Despite the continual progress in cancer treatment, high toxicity and resistance to therapy remain recurring challenges. Croton grewioides Baill. is a plant from the brazilian semi-arid region with significant pharmacological potential due to its reported antidiarrheal, antioxidant, and antitumor properties. This study evaluated the antitumor activity of the essential oil from C. grewioides leaves (CgEO) by in vitro assays. CgEO showed higher cytotoxicity in human melanoma cells (SK-MEL-28), with a 50% inhibitory concentration (IC50) of 70.0 μg/mL after 72 hours, but with low toxicity in healthy keratinocytes (HaCaT). Additionally, it was suggested that the antitumor effect of CgEO is associated with the induction of apoptosis, cell cycle alterations, and combined antioxidant action mechanisms. In conclusion, CgEO exhibits antitumor activity with lower toxicity in non-tumor cells.

Clonal evolution: a landmark of MPN evolution

Myeloproliferative Neoplasms comprise a heterogeneous group of diseases characterized over the past two decades by the acquisition of somatic mutations in hematopoietic stem cells, leading to a pre-leukemic state. The natural history of the disease is marked by the sequential acquisition of genetic events that play an essential role in the phenotype, evolution and response to treatment of the disease. Indeed, disease progression is as heterogeneous as the variety of genetic abnormalities found in individual patients, some of whom lead to disease evolution with a pejorative prognosis, while others persist in a benign manner. In order to better explore these questions, it is important to better understand: (1) the genetic structure of the tumor through dynamic reconstruction of clonal architecture (2) the factors favoring the development of certain clones and their expansion, some of which are governed by Darwinian laws. These parameters could help explain the heterogeneity between MPN patients with similar genetic profiles, and prevent the emergence of clones identified as aggressive by the use of innovative therapeutic strategies targeting new pathways to prevent early transformations in poor prognosis MPN subtypes.

Comparative study for fatigue prevalence in subjects with diseases: a systematic review and meta-analysis

Fatigue is one of the common symptoms in individuals with diseases or disorders, significantly affecting quality of life (QoL) and the prognosis of diseases. This study aimed to comprehensively compare the features of fatigue across a wide range of diseases. We systematically searched the PubMed and Cochrane Library databases from inception to March 31st, 2021, and conducted a meta-analysis to generate precise estimates. The analyses were stratified by classification of diseases, gender, and severity of fatigue (moderate and severe), and study quality was assessed using the Newcastle–Ottawa Scale (NOS). In total, 214 articles (233 prevalence data) met our eligibility criteria, covering 102,024 participants (mean 438 ± 1,421) across 88 diseases. Among these, seventy-eight data sets (52,082 participants) and thirty-nine data sets (10,389 participants) reported gender- and severity-related fatigue prevalence. The overall prevalence among subjects with 88 diseases was 49.4% [95% CI 46.9–52.1]. According to the International Classification of Diseases-10 (ICD-10) classification, the highest prevalence of fatigue (65.9% [95% CI 54.9–79.6]) was observed in patients with mental/behavioral diseases, whereas the lowest prevalence (34.7% [95% CI 24.5–49.2]) was found among those with circulatory system diseases. A slight female dominance (43.5% vs. 49.8%) was observed in the total data, with the most notable female predominance (1.8-fold) seen in patients with low back pain. The top disease groups with a moderate to severe level of fatigue included gastroparesis (92.3%), pulmonary hypertension (90.0%), chronic obstructive pulmonary disease (COPD, 83.2%), and multiple sclerosis (80.0%). These results are the first to comprehensively show the comparative features of fatigue prevalence among subjects across 88 diseases. Our findings provide valuable reference data for future research on fatigue and for the management of patients with fatigue.Prospero registration number: CRD42021270494

Disease Associations among Patients Afflicted with Both Glaucoma and Age-Related Macular Degeneration

Background/Objectives: This study investigates whether there is an increased propensity to systemic conditions in patients with both age-related macular degeneration (AMD) and glaucoma in order to provide greater insight into patients’ overall health and response to physiologic stress. Methods: A large retrospective dataset review was conducted between April 2004 and June 2018, distinguishing four groups based on international classification of diseases (ICD) codes: glaucoma only, AMD only, glaucoma and AMD, and cataracts only (as an age-matched control). The systemic disease prevalence of each group was calculated, and a Friedman analysis was used to compare the prevalence between the groups. Results: This study identified 5243 patients with glaucoma only, 6726 with AMD only, 402 with combined disease, and 25,450 with cataracts only. Age and racial distributions varied between groups in a predictable manner. Two conditions, heart failure (HF) and dementia, had a statistically higher prevalence in patients with both glaucoma and AMD compared to those with glaucoma alone (HF p = 0.036, dementia p = 0.024) and cataracts alone (HF p = 0.003, dementia p = 0.036). There was no significant difference observed in terms of ethnicity and gender among the different disease groups (p &gt; 0.05). Conclusions: Both AMD and glaucoma individually portend a higher rate of comorbidities than age-matched controls. Patients with concomitant AMD and glaucoma demonstrate a uniquely higher prevalence of heart failure and dementia than those with either disease alone. The underlying association and pathologic mechanisms warrant further investigation to improve the overall health management and prognostication for these individuals.

Anterior Optic Neuropathies without Optic Disc Edema

Anterior optic neuropathies in which the optic discs appear normal include nutritional optic neuropathy, vitamin B12 or folate deficiencies, toxic optic neuropathy due to drugs and heavy metals, and hereditary optic neuropathy. When these conditions become chronic, optic atrophy can occur. Treatment of these diseases, which can cause dramatic vision loss, should be done quickly and permanent neuronal damage should be prevented as much as possible. Therefore, this group of diseases should always be kept in mind by clinicians in cases of unexplained visual loss.

Vulnerability of neurofilament-expressing neurons in frontotemporal dementia

Frontotemporal dementia (FTD) is an umbrella term for several early onset dementias, that are caused by frontotemporal lobar degeneration (FTLD), which involves the atrophy of the frontal and temporal lobes of the brain. Neuron loss in the frontal and temporal lobes is a characteristic feature of FTLD, however the selective vulnerability of different neuronal populations in this group of diseases is not fully understood. Neurofilament-expressing neurons have been shown to be selectively vulnerable in other neurodegenerative diseases, including Alzheimer's disease and amyotrophic lateral sclerosis, therefore we sought to investigate whether this neuronal population is vulnerable in FTLD. We also examined whether neuronal sub-type vulnerability differed between FTLD with TDP-43 inclusions (FTLD-TDP) and FTLD with tau inclusions (FTLD-Tau). Post-mortem human tissue from the superior frontal gyrus (SFG) of FTLD-TDP (n = 15), FTLD-Tau (n = 8) and aged Control cases (n = 6) was immunolabelled using antibodies against non-phosphorylated neurofilaments (SMI32 antibody), calretinin and NeuN, to explore neuronal cell loss. The presence of non-phosphorylated neurofilament immunolabelling in axons of the SFG white matter was also quantified as a measure of axon pathology, as axonal neurofilaments are normally phosphorylated. We demonstrate the selective loss of neurofilament-expressing neurons in both FTLD-TDP and FTLD-Tau cases compared to aged Controls. We also show that non-phosphorylated neurofilament axonal pathology in the SFG white matter was associated with increasing age, but not FTLD. This data suggests neurofilament-expressing neurons are vulnerable in both FTLD-TDP and FTLD-Tau.

12362 Pathophysiology From Oxidative Stress Effectively Monitored In A Pre-clinical Model Of Type 2 Diabetes (T2D) With Point-of-care Microscale Magnetic Resonance (µNMR)

Abstract Disclosure: A.T. Alves: ; Co-Founder. ; Self. ; LarmorBio. S.S. Thamarath: ; Co-Founder. ; Self. ; LarmorBio. S. Fjordside: Employee; Self; Novo Nordisk. S. Sassower, MS.EE: ; Co-Founder. ; Self. ; LarmorBio. J. Han: None. L. Bouchard: Advisory Board Member; Self; LarmorBio. R. Rohr, BS.EE: ; Co-Founder, CEO. ; Self. ; LarmorBio. A.P. Chambers: Employee; Self; Novo Nordisk. The declining age of onset of T2D is a vital factor influencing its prospective burden. An early manifestation of the disease leads to an extended duration, which amplifies and accelerates the risk of micro and macrovascular complications. Oxidative stress is a major driver in the pathogenesis of T2D. Early detection and prevention of oxidative stress overload can improve and potentially modify the long-term harmful outcomes of metabolic diseases, including chronic hyperglycaemia.A novel µNMR assay was developed to monitor oxidative stress from minimally invasive plasma samples at the point of care. This approach is highly sensitive to redox changes in the blood microenvironment, including increased ferric iron (Fe3+), protein oxidation, and lipid peroxidation[1]. We hypothesized that oxidative stress would increase significantly faster in the disease group, enabling disease progression monitoring throughout the study and near real-time subject risk stratification based on the core pathophysiology of the diabetic phenotype.This 15-week longitudinal study (6th - 21st week of age) quantified oxidative stress in db/db and db/+ mice (n = 15 per group), accompanied by HbA1c, blood glucose (BG), and body weight (BW). The assay detailed separation (P ≤ 0.01) between the db/db and db/+ mice from the onset of the diabetic phenotype of db/db at 10 weeks of age (mean HbA1c = 6.5%). The oxidative stress monitored continued to increase in the subsequent weeks, where the HbA1c of db/db mice reached maximum (mean HbA1c = 8.8%). The definition of good (HbA1c ≤ 8) and poor (HbA1c &amp;gt; 8) glycaemic control was defined where sub-stratification (P ≤ 0.05) was achieved. Furthermore, the assay highlights a positive correlation with BW (ρ+/db = 0.52, P ≤ 0.0001, ρdb/db = 0.57, P ≤ 0.0001). In the two groups of mice, a positive correlation of oxidative stress with HbA1c (ρ = 0.58, P ≤ 0.0001) and BG (ρ = 0.47, P ≤ 0.0001) was reported. During the 15-week study, the control db/+ group exhibited a 13% mean increase in oxidative stress. In contrast, the db/db group demonstrated a cumulative 20% increase. Notably, considering the diabetic phenotype of the db/db mice, we quantified oxidative stress attributed to aging at 13%.In view of changing diabetes demographics, a multimodal approach of targeted sub-phenotype treatment combined with advanced metabolic monitoring may provide holistic, clinically relevant information to reduce the micro and macrovascular burden of diabetes. In summary, the µNMR assay is an effective method for real-time monitoring of oxidative stress assessment in metabolic disease research and opens new possibilities for cardiometabolic risk assessment and targeted interventions.(1) Peng, W.K. et.al., npj Aging Mech Dis 2020, 6, 11 Presentation: 6/1/2024

A sensitive immunoassay for the quantitation of Pig-MAP in pig saliva samples

The purpose of the study is to develop a sensitive assay for the proper quantification of the acute phase protein Pig-MAP in pig saliva samples. A time-resolved immunofluorometric assay (TR-IFMA) was developed using two pig-MAP-specific monoclonal antibodies. The limit of detection of the assay was 4 ng/mL, enough to measure pig-MAP concentration in saliva. Precision was evaluated for saliva samples of low, medium and high concentration, with inter assay CV of 4–14 % and inter-assay CV of 8–20 %. The assay kept linearity under dilution and a method comparison study performed with serum samples showed good correlation with ELISA. Median Pig-MAP concentration in saliva from healthy animals was 19 ng/mL whereas in pigs with different inflammatory conditions was 11 times higher. In the same animals median pig-MAP serum concentrations were 0.72 mg/mL in the healthy group and 4.61 in the diseased group. The Spearman coefficient of correlation between Pig-MAP concentration in serum and saliva was of 0.72. A correlation was also observed between the salivary concentration of pig-MAP and other two acute phase proteins such as haptoglobin (r = 0.62) or C-reactive protein (r = 0.65). The concentration of Pig-MAP in saliva of pigs with severe respiratory disease decreased significantly from a median value of 128 ng/mL at the time of disease detection to 8 ng/mL after 1 day of antibiotic therapy. Studies performed show that pig-MAP is present in saliva and this specimen may be an alternative to serum for pig-MAP quantification.

5174 A longitudinal retrospective cohort study on the application of the Superimposition by translation and rotation (SITAR) model to estimate body composition growth trajectory in Korean children and adolescents during puberty

Abstract Disclosure: S. Kim: None. S. Kim: None. J. Suh: None. Introduction: In addition to adulthood, pediatricians have noted a growing emphasis on research concerning sarcopenic obesity. Studies in this field have expanded beyond basic BMI-related inquiries, actively delving into investigations based on body fat mass (BFM) and fat-free mass (FFM). However, limited research has systematically analyzed the acquisition of body composition during children and adolescence based on longitudinal data. Objective: This study aims to assess the acquisition of weight, FFM, and BFM during the pubertal growth of Korean children and adolescents. Methods: This study utilized mixed longitudinal body measurement and body composition data, employing bioelectrical impedance analysis, from 4,641 height measurements (2,204 for boys and 2,437 for girls) obtained from 361 individuals (170 boys and 191 girls) among Korean children and adolescents aged 7 to 18. The SITAR (the Superimposition by Translation and Rotation) model, a shape-invariant growth curve model, was used to estimate a reference height velocity curve during pubertal growth. Results: The SITAR methodology allowed us to investigate the timing, magnitude, and intensity of adolescent weight, FFM, and BFM gain. The results revealed significant differences in growth trajectories between boys and girls, with boys exhibiting a persistent elevation in FFM and a pattern of ascent followed by a decline in BFM, while girls show an increase in BFM and a deceleration in FFM growth. In Korean boys, the peak weight velocity (PWV) occurred at a mean age of 12.41 years, with a rate of 8.19 kg/year. Peak fat-free mass velocity (PFV) was observed at a mean age of 9.69 years, with a rate of 7.60 kg/year, and peak body fat mass velocity (PBV) at a mean age of 12.70 years, with a rate of 2.67 kg/year. In Korean girls, the mean age of PWV was 11.28 years, with a velocity of 6.33 kg/year. PFV occurred at a mean age of 12.33 years, with a rate of 4.86 kg/year, and PBV at a mean age of 11.13 years, with a rate of 2.72 kg/year. The ages of peak velocities of height (PHV), PWV, PFV, and PBW positively correlated. Conclusions: This study is the first to apply the SITAR model to examine the acquisition of body composition in Korean children and adolescents. Future research should delve into exploring the connections between various disease groups during childhood and adolescence and the patterns of change in body composition. Presentation: 6/1/2024

6453 Cushing Syndrome And Bilateral Adrenal Incidentalomas In A Patient With Mucopolysaccharidosis

Abstract Disclosure: D. John: None. M. Kinaan: None. TITLE Cushing Syndrome &amp; Bilateral Adrenal Incidentalomas in a patient with Mucopolysaccharidosis Affiliation of Authors Dieula John M.D., M.B.A.,a,b Mustafa Kinaan M.D.,a,baEndocrinology, Diabetes, and Metabolism Fellowship, UCF HCA Healthcare GME, Orlando, FL. bDepartment of Internal Medicine, UCF College of Medicine, Orlando, FL. This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Introduction: Mucopolysaccharidoses (MPS) is a group of hereditary and incurable storage diseases characterized by a deficiency of enzymes involved in the metabolism of glycosaminoglycans (GAGs) at the lysosomal level. MPS are usually inherited in autosomal recessive or x-linked pattern. MPS affects functioning of the cells, tissues and organs where the GAGs products typically accumulate. This can result in neurologic, developmental, and neoplastic issues. While endocrine disturbances in MPS have been reported, the literature on hypercortisolism and adrenal masses in MPS is limited. We present a case of a patient with MPS diagnosed with Cushing Syndrome (CS) as part of evaluation for adrenal incidentalomas. Case Description: A 50 year old male with a medical history of MPS, DVT, and developmental delay presented to our clinic accompanied by his mother for evaluation of adrenal incidentalomas. CT abdomen incidentally showed a left adrenal non-calcified, non-hemorrhagic mass measuring 3.9 x 3.6 cm with a pre-contrast attenuation of 45 Hounsfield units. Delayed washout was not obtained, and washout calculation couldn’t be performed. These radiologic features were suspicious for malignancy. Repeat CT with adrenal protocol showed left adrenal mass measuring 4.5 x 3.9 cm with central necrosis, unenhanced attenuation of 42 HU, and no drop-in attenuation on delayed phase indicating poor absolute and relative washout. There was also a right adrenal mass measuring up to 2.2 cm 54.5% absolute washout and 39.0% relative washout. Biochemical workup showed no pheochromocytoma, hyperaldosteronism, or adrenal hyperandrogenism. However, his dex suppression test was consistent with ACTH-independent CS. The patient was referred to an endocrine surgeon. We anticipate more information to be available based on the pathology of the excised tumor following his urgent surgery. Conclusion: MPS diseases are extremely rare and their effects on the endocrine system in general, and the adrenal gland specifically, is limited. Our case would serve as the first reported case of CS in MPS patient based on our literature search. In addition, we’ll discuss the pathology findings once the tumor is excised and highlight the connection between the adrenal mass and this lysosomal storage disease. Presentation: 6/3/2024

Posterior Optic Neuropathies

Posterior optic neuritis refers to a group of rarer diseases of optic neuritis. Similar to anterior optic neuropathies, they can cause decreased visual acuity and optic nerve dysfunction. Although they can be caused by various causes, corticosteroids are important in their treatment. A multidisciplinary approach with ophthalmologists may be required in their management.

Role and Function of Peroxisomes in Neuroinflammation.

Peroxisomes are organelles involved in many cellular metabolic functions, including the degradation of very-long-chain fatty acids (VLCFAs; C ≥ 22), the initiation of ether-phospholipid synthesis, and the metabolism of reactive oxygen species. All of these processes are essential for the maintenance of cellular lipid and redox homeostasis, and their perturbation can trigger inflammatory response in immune cells, including in the central nervous system (CNS) resident microglia and astrocytes. Consistently, peroxisomal disorders, a group of congenital diseases caused by a block in peroxisomal biogenesis or the impairment of one of the peroxisomal enzymes, are associated with neuroinflammation. Peroxisomal function is also dysregulated in many neurodegenerative diseases and during brain aging, both of which are associated with neuroinflammation. This suggests that deciphering the role of peroxisomes in neuroinflammation may be important for understanding both congenital and age-related brain dysfunction. In this review, we discuss the current advances in understanding the role and function of peroxisomes in neuroinflammation.