Elevated Creatine Kinase Levels Research Articles

Serum Biochemical Parameters of Broilers Affected by Wooden Breast Myopathy.

Wooden breast (WB) myopathy is a pathology of the pectoralis major muscle. Wooden breast is caused by multiple factors. The exact etiopathogenesis of this myodegenerative pathology is still unclear. Fast-growing commercial lines of broilers that are selected for high breast muscle yields are more susceptible to this myopathy. The biochemical analysis of blood is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of Ross 308 chicken broilers without myopathy and those affected by WB myopathy. Blood samples were collected from male and female Ross 308 broilers that were 43 days old, with an average live weight of 2.98-3.09 kg. Representative blood samples were selected from broilers with WB (n = 33) and without WB (n = 33). In the laboratory, the blood was centrifugated, and biochemical tests were performed with an automated computerized biochemistry analyzer. The research results showed that broilers with WB had elevated blood serum levels of creatine kinase (CK) (p = 0.018), potassium (p = 0.010), and alanine aminotransferase (ALT) (p = 0.012). In conclusion, elevated serum levels of CK and potassium indicated that skeletal muscle cells were damaged. Moreover, increased ALT levels suggested a possible association between WB myopathy and liver damage. Additionally, these research findings underscore the diagnostic significance of CK and hint at its potential as a WB biomarker.

Six Years Follow-Up of an 11-Year-Old Girl with Anti-HMGCR Myopathy.

Anti-HMGCR myopathy is decribed as an immune-mediated necrotizing myopathy which is characterised by subacute, progressive proximal muscle weakness and elevated creatine kinase (CK) level. In pediatric population, anti-HMGCR myopathy has been reported solely as small case reports, albeit rare. Although treatment consensus has not yet been established, proper treatment with several immunomodulators to include IVIg can show remarkable improvement. We report an 11-year-old-girl diagnosed with anti-HMGCR myopathy with 6 years of follow-up.

Surveillance for rhabdomyolysis after the consumption of crayfish in Wuhan, China, 2016-2022.

To analyze the epidemiological characteristics and etiology of crayfish-related rhabdomyolysis. Cases of crayfish-related rhabdomyolysis in Wuhan were monitored, and professional training of city's surveillance personnel was conducted. Unified questionnaires were used to collect data. The first case of crayfish-related rhabdomyolysis occurred on July 12, 2016. Subsequently, 423 patients were reported over the next 7 years, with muscle pain, weakness, and chest distress as main symptoms. In total, 64.54% (273/423) of patients were females, and young adults (aged 20-49 years) account for 86.22% (363/423) of patients. The primary clinical presentations were muscle pain, muscle weakness, and chest discomfort. The median incubation time was 6 h. And the number of cases may be related to water levels in Yangzi river. Laboratory tests revealed elevated creatine kinase and myoglobin levels. In total, 95.16% (236/248) of patients had consumed crayfish tail shrimp and 91.53% (227/248) had consumed crayfish liver and pancreas (Female crayfish also contain ovaries). Only 25.00% (62/248) of patients had a history of alcohol consumption. On average, 227 patients consumed 15 (3-50) crayfish, of whom 84.14% (191/227) consumed more than 10 crayfish. All patients had a favorable prognosis. Crayfish-related rhabdomyolysis is a kind of a case or cluster of patients present with severe myalgia or weakness of unknown etiology and mechanism disease in Wuhan, China, 2016-2022. Excessive consumption of crayfish may be a risk factor for the disease. The relationship between the specific parts of crayfish consumed and the onset of the disease is unclear, suggesting further research is needed to identify the relevant risk factors for the disease.

Immune-Mediated Necrotizing Myopathy

Immune-mediated necrotizing myopathy (IMNM) is a form of autoimmune myositis characterized by the presence of necrotic and regenerating process as a major finding in the muscle. Anti-SRP and anti-HMGCR have been identified as IMNM-specific autoantibodies. Patients with this disease often present with severe muscle weakness and markedly elevated serum creatine kinase (CK) levels. Differentiation from muscular dystrophy is challenging in certain cases. When patients meet the condition "subacute onset", "hyperCKemia over 1000 IU/L", and "clinical diagnosis of muscular dystrophy lacking molecular diagnosis", the possibility of IMNM should be considered. Autoantibody measurement, including of anti-SRP and HMGCR antibodies, is recommended. Treatment with corticosteroid in combination with immunosuppressants, intravenous immunoglobulin, and rituximab can be performed.

Aripiprazole-induced quasi-neuroleptic malignant syndrome: two case reports

BackgroundSignificant elevation of creatine kinase levels (above three digits) and leucocytosis in the absence of muscle rigidity, tremors, or autonomic dysfunction can pose a real challenge in the context of antipsychotic treatment as an early herald of neuroleptic malignant syndrome.Case presentationWe present here two cases of adult male patients of Black British heritage, ages 51 years and 28 years, respectively. Both received a diagnosis of schizoaffective disorder and presented with massive increase of creatine kinase blood level after aripiprazole depot administration, one with pernicious increase associated with silent neuroleptic malignant syndrome, and the second with asymptomatic benign enzyme elevation.ConclusionThough aripiprazole use is less likely to cause neuroleptic malignant syndrome, on rare occasions it can produce massive symptomatic or asymptomatic increase in serum creatine kinase enzyme levels, raising the need for close monitoring, especially at the initial doses of the drug.

Immune-Mediated Necrotizing Myopathies: Current Landscape.

Immune-mediated necrotizing myopathy (IMNM), characterized by acute or subacute onset, severe weakness, and elevated creatine kinase levels, poses diagnostic and therapeutic challenges. This article provides a succinct overview of IMNM, including clinical features, diagnostic strategies, and treatment approaches. Recent insights highlight the different clinical presentations and therapeutic options of IMNM stratified by autoantibody positivity and type. Additionally, recent findings call into question the reported link between statin use and IMNM. This review synthesizes current knowledge on IMNM, emphasizing its distinct clinical features and challenging management. The evolving understanding of IMNM underscores the need for a comprehensive diagnostic approach that utilizes a growing range of modalities. Early and aggressive immunomodulatory therapy remains pivotal. Ongoing research aims to refine diagnostic tools and therapeutic interventions for this challenging muscle disorder, underscoring the importance of advancing our understanding to enhance patient outcomes.

Idebenone ameliorates statin-induced myotoxicity in atherosclerotic ApoE−/− mice by reducing oxidative stress and improving mitochondrial function

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE−/− mice and whether idebenone could counteract it. After administering simvastatin to ApoE−/− mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

Nationwide survey of patients with multisystem proteinopathy in Japan.

Multisystem proteinopathy (MSP) is an inherited disorder in which protein aggregates with TAR DNA-binding protein of 43 kDa form in multiple organs. Mutations in VCP, HNRNPA2B1, HNRNPA1, SQSTM1, MATR3, and ANXA11 are causative for MSP. This study aimed to conduct a nationwide epidemiological survey based on the diagnostic criteria established by the Japan MSP study group. We conducted a nationwide epidemiological survey by administering primary and secondary questionnaires among 6235 specialists of the Japanese Society of Neurology. In the primary survey, 47 patients with MSP were identified. In the secondary survey of 27 patients, inclusion body myopathy was the most common initial symptom (74.1%), followed by motor neuron disease (11.1%), frontotemporal dementia (FTD, 7.4%), and Paget's disease of bone (PDB, 7.4%), with no cases of parkinsonism. Inclusion body myopathy occurred most frequently during the entire course of the disease (81.5%), followed by motor neuron disease (25.9%), PDB (18.5%), FTD (14.8%), and parkinsonism (3.7%). Laboratory findings showed a high frequency of elevated serum creatine kinase levels and abnormalities on needle electromyography, muscle histology, brain magnetic resonance imaging, and perfusion single-photon emission computed tomography. The low frequency of FTD and PDB may suggest that FTD and PDB may be widely underdiagnosed and undertreated in clinical practice.

Imatinib pharmacokinetics and creatine kinase levels in chronic myeloid leukemia patients: implications for therapeutic response and monitoring.

Imatinib treatment for certain cancers can lead to elevated creatine kinase (CK) levels, potentially indicating muscle injury, and ongoing research aims to understand the correlation between imatinib levels and creatine kinase to assess its impact on treatment response. This single-center observational study involved 76 chronic myeloid leukemia (CML) patients receiving imatinib treatment, focusing on evaluating drug and metabolite levels using liquid chromatography-mass spectrometry (LC-MS-MS) instrumentation. Serum CK and creatine kinase-MB (CK-MB) levels were assessed using Colorimetric kits. CK and CK-MB levels were measured, CK showed a median value of 211.5 IU/l and CK-MB showed a median value of 4.4 IU/l. Comparing low and high CK groups, significant differences were found in peak and trough plasma concentrations of imatinib and its metabolites. Correlations between CK levels and pharmacokinetic parameters were explored, with notable associations identified. Binary logistic regression revealed predictors influencing the therapeutic response to imatinib and categorized expected CK levels into high or low, with peak levels of imatinib emerging as a significant predictor for CK level categorization. The study highlights the link between imatinib's pharmacokinetics and elevated CK levels, indicating a possible correlation between specific metabolites and improved treatment response. Individualized monitoring of CK levels and imatinib pharmacokinetics could enhance care for CML patients.

An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?

SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T>G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia.

Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies

BackgroundPathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies.MethodsNine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them.ResultsThree of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively.ConclusionOur study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

Copper Intoxication in South American Camelids-Review of the Literature and First Report of a Case in a Vicuña (Vicugna vicugna).

Copper (Cu), an essential trace element in the metabolism of mammals, plays a central role in various metabolic processes. However, overdosing can lead to severe symptoms and even fatalities. Chronic Cu intoxication continues to be a problem in grazing and domestic animals, with sheep being particularly sensitive. There are few comparative studies on its impact on South American camelids (SACs). Therefore, this work presents the results of literature research combined with a case report on a 3-year-old female vicuña (Vicugna vicugna) presented to the clinic from a zoological garden in northern Germany. The animal showed reduced food intake, recumbency, bruxism, icteric mucous membranes and sclera. Auscultation revealed atony of the third compartment and the digestive tract. Similar to cases described in the literature, the animal showed rapid deterioration of its condition with unspecific symptoms of liver failure and rapid death. However, in contrast to descriptions in sheep, clinical icterus has not been previously reported in cases of other SACs. Laboratory findings from EDTA and serum samples revealed neutrophilia with a left shift, hypoproteinaemia, lymphopaenia, azotaemia, elevated levels of creatine kinase (CK), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) in the serum. Hyperbilirubinaemia and significantly elevated serum and liver Cu levels were observed. Subsequent blood samples from the remaining vicuñas and alpacas in the same enclosure showed no remarkable abnormalities. To the best of the authors' knowledge, this case report represents the first documented case of Cu intoxication specifically in vicuñas.

Evaluation of a New Cystoscopic Cryocatheter and Method for the In Situ Destruction of Bladder Cancer: Preliminary In Vivo Study.

Purpose: To assess the ability to deliver full-thickness bladder wall cryoablation through a cystoscopic approach using a new closed-loop 6F cryocatheter and thermal dose-controlled protocol. Materials and Methods: Evaluations were conducted using a chronic porcine model wherein 10 lesions/animal were created throughout the bladder (bladder wall, trigone region, ureteral orifice, and distal ureter). A 6F cryocatheter was passed through the working channel of a flexible cystoscope. Single 1- and 1.5-minute freeze protocols in a saline environment were evaluated and resultant lesion size was determined. A laparoscopic approach was utilized to observe the transmural extension of the ice propagation. Results: Studies demonstrated the generation of transmural lesions characterized by full-thickness histologic necrosis after freezing for 1.5 minutes regardless of tissue thickness (range 2-12 mm). All animals were found to have good overall health (maintained weight, appetite, mobility, and energy levels) throughout the recovery period. No significant deviations were noted in complete blood count and serum chemistry bloodwork except for elevated creatine kinase levels. Importantly, no fistulas or perforations were noted. Conclusions: The cryocatheter was able to rapidly and effectively freeze the bladder wall through a cystoscopic approach. The results showed the ability to consistently ablate an ∼1 cm diameter and up to 1.2 cm deep using a single 1.5-minute freeze protocol. Analysis of the ablation efficacy revealed ∼80% destruction within the frozen mass. Although further testing and refinement are needed, these studies demonstrate the potential of this new approach to provide a next-generation strategy for the treatment of bladder cancer.

Statin Myopathy: A Case series

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy (anti-HMGCR IMNM) is a rare adverse effect associated with the use of statin medications [1]. While the investigation remains ongoing, statin exposure is thought to induce mitochondrial dysfunction due to inhibition of HMGCR, subsequently triggering an inflammatory cascade with oxidative stress and autoantibodies (aAbs) against HMGCR, ultimately leading to an immune-mediated necrotizing myopathy (IMNM) [2]. Clinical presentation may involve dermatomyositis-like features ranging from myalgias to severe and progressive proximal muscle weakness, often persisting after cessation of the offending statin [3]. Serum studies typically reveal significantly elevated Creatine Kinase (CK) levels, often ranging from 10 to 100 times the upper limit of normal [4]. Presumptive diagnosis is confirmed via muscle biopsy, which typically reveals necrotic fibers with minimal inflammatory cell infiltrates [5]. In addition to withdrawal of the offending agent, treatment may involve immunomodulatory medications (e.g. intravenous immunoglobulin (IVIG), steroids, and/or Rituximab). For most patients, resolution typically occurs over months, sometimes years. This paper highlights three cases of statin-induced myopathy and the clinical implications for providers in prompt recognition, diagnosis, and management of this rare condition. Further research is needed to better understand both the risk factors and underlying mechanisms in order to increase awareness, optimize care, and minimize the morbidity associated with this adverse drug reaction.

A female patient carrying a novel DMD mutation with non-random X-chromosome inactivation from a DMD family

ObjectiveTo analyze the clinical phenotype and genetic characteristics of a female proband carrying a novel mutation in the DMD gene with non-random X-chromosome inactivation in a large pedigree with pseudohypertrophic muscular dystrophy.MethodsClinical information of the female proband, her monozygotic twin sister, and other family members were collected. Potential pathogenic variants were detected with Multiplex Ligation-dependent Probe Amplification (MLPA) and whole-exome sequencing (WES). Methylation-sensitive restriction enzyme (HhaI) was employed for X-chromosome inactivation analysis.ResultsThe proband was a female over 5 years old, displayed clinical manifestations such as elevated creatine kinase (CK) levels and mild calf muscle hypertrophy. Her monozygotic twin sister exhibited normal CK levels and motor ability. Her uncle and cousin had a history of DMD. WES revealed that the proband carried a novel variant in the DMD (OMIM: 300,377) gene: NM_004006.3: c.3051_3053dup; NP_003997.2: p.Tyr1018*. In this pedigree, five out of six female members were carriers of this variant, while the cousin and uncle were hemizygous for this variant. X-chromosome inactivation analysis suggested non-random inactivation in the proband.ConclusionThe c.3051_3053dup (p.Tyr1018*) variant in the DMD gene is considered to be the pathogenic variant significantly associated with the clinical phenotype of the proband, her cousin, and her uncle within this family. Integrating genetic testing with clinical phenotype assessment can be a valuable tool for physicians in the diagnosis of progressive muscular dystrophies, such as Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD).

Caregiver Burden with Duchenne and Becker Muscular Dystrophy in Japan: A Clinical Observation Study.

Objective Skeletal muscle weakness and cardiomyopathy can be seen in carriers of dystrophinopathy. Therefore, the health management of caregivers of Duchenne/Becker muscular dystrophy (DMD/BMD) patients who are themselves carriers is an important issue. However, few studies have focused on caregivers who have dystrophin mutations. Methods In this cross-sectional study conducted at five hospitals, the daily living, situation medical treatment status, genetic testing, physical assessment, care burden, and quality of life of caregivers of DMD/BMD patients were surveyed. Results The subjects were 36 main caregivers (mean age 55.7±8.4 years old), of whom 52.8% were diagnosed as carriers, 8.3% were noncarriers, and 38.9% were not confirmed. In addition, half of the caregivers were not examined regularly at medical institutions. Of all caregivers, 54.3% had muscle or cardiac symptoms, and 75% had elevated serum creatine kinase levels. The mean Zarit Caregiver Burden Interview (ZBI) total score of current caregivers was 20.9±13.1. The frequency of a ZBI total score ≥25 was significantly higher in caregivers diagnosed as carriers than in caregivers unexamined as carriers (p=0.04). The health-related quality of life score (Short Form 36; SF-36) in caregivers was slightly lower than the Japanese standard scores in the sections of physical functioning, role limitations-physical, bodily pain, and social functioning. Conclusion Some caregivers of DMD/BMD patients can themselves have muscular or cardiac symptoms and a heavy care burden. It is therefore necessary for carrier caregivers, especially women, to undergo regular health checkups and receive appropriate health management.

Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation with rapidly progressive muscular weakness and elevated levels of creatine kinase, while traditional pharmacological approaches possess varying and often limited effects. Considering the pathogenic role of autoantibodies, chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA) have emerged as a promising therapeutic strategy. We reported here a patient with anti-signal recognition particle IMNM refractory to multiple available therapies, who was treated with BCMA-targeting CAR-T cells, exhibited favorable safety profiles, sustained reduction in pathogenic autoantibodies, and persistent clinical improvements over 18 mo. Longitudinal single-cell RNA, B cell receptor, T cell receptor sequencing analysis presented the normalization of immune microenvironment after CAR-T cell infusion, including reconstitution of B cell lineages, replacement of T cell subclusters, and suppression of overactivated immune cells. Analysis on characteristics of CAR-T cells in IMNM demonstrated a more active expansion of CD8+ CAR-T cells, with a dynamic phenotype shifting pattern similar in CD4+ and CD8+ CAR-T cells. A comparison of CD8+ CAR-T cells in patients with IMNM and those with malignancies collected at different timepoints revealed a more NK-like phenotype with enhanced tendency of cell death and neuroinflammation and inhibited proliferating ability of CD8+ CAR-T cells in IMNM while neuroinflammation might be the distinct characteristics. Further studies are warranted to define the molecular features of CAR-T cells in autoimmunity and to seek higher efficiency and longer persistence of CAR-T cells in treating autoimmune disorders.

Recent Advances and Updates in Rhabdomyolysis: A Comprehensive Review

Rhabdomyolysis (RML) is a complex clinical syndrome marked by the breakdown of skeletal muscle cells, with historical recognition dating back to biblical times and modern understanding evolving since World War II. This comprehensive review explores the diverse landscape of RML, encompassing its epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis. As a result of trauma or non-traumatic muscle injuries, pathogenesis involves the release of intracellular components into the bloodstream. Epidemiologically, RML exhibits demographic nuances, emphasizing the importance of recognizing risk factors for prevention. Clinical manifestations range from the classic triad of muscle pain, weakness, and dark urine to diverse presentations. Diagnosis involves evaluating elevated creatine kinase levels and myoglobinuria, with management strategies focusing on fluid balance, AKI prevention, and addressing underlying causes. The prognosis is diverse, influenced by complications such as AKI, with various scoring systems aiding risk assessment. Prevention and treatment strategies include a multifaceted approach, integrating tailored warm-ups, mindful exercise, education, and dietary modifications. Overall, the prognosis for RML remains favorable, underscoring the significance of meticulous management. This review provides a comprehensive understanding of RML, bridging historical insights with contemporary medical strategies and guiding ongoing research and advancements in patient care for this intricate condition. RML serves as a paradigm for integrating nuanced historical perspectives and modern medical approaches, highlighting the intricate balance required for effective management in clinical practice.

Recent Advances and Updates in Rhabdomyolysis: A Comprehensive Review

Rhabdomyolysis (RML) is a complex clinical syndrome marked by the breakdown of skeletal muscle cells, with historical recognition dating back to biblical times and modern understanding evolving since World War II. This comprehensive review explores the diverse landscape of RML, encompassing its epidemiology, etiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis. As a result of trauma or non-traumatic muscle injuries, pathogenesis involves the release of intracellular components into the bloodstream. Epidemiologically, RML exhibits demographic nuances, emphasizing the importance of recognizing risk factors for prevention. Clinical manifestations range from the classic triad of muscle pain, weakness, and dark urine to diverse presentations. Diagnosis involves evaluating elevated creatine kinase levels and myoglobinuria, with management strategies focusing on fluid balance, AKI prevention, and addressing underlying causes. The prognosis is diverse, influenced by complications such as AKI, with various scoring systems aiding risk assessment. Prevention and treatment strategies include a multifaceted approach, integrating tailored warm-ups, mindful exercise, education, and dietary modifications. Overall, the prognosis for RML remains favorable, underscoring the significance of meticulous management. This review provides a comprehensive understanding of RML, bridging historical insights with contemporary medical strategies and guiding ongoing research and advancements in patient care for this intricate condition. RML serves as a paradigm for integrating nuanced historical perspectives and modern medical approaches, highlighting the intricate balance required for effective management in clinical practice

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.