Increased Serum Creatine Kinase Research Articles

Neuropathology of Severe Depression in Long COVID-19 Infection; Possible Roles for Astrocytes, Creatine Kinase and Lactate Dehydrogenase Activity

Background: The incidence of depression has increased significantly during the COVID-19 pandemic. Some individuals infected with COVID-19 develop persistent neurological and neuropsychiatric symptoms approximately 12 weeks after the acute infection, a condition known as long COVID-19 syndrome. However, the underlying pathogenesis remains unclear. Glial fibrillary acidic protein (GFAP), creatine kinase (CK), and lactate dehydrogenase (LDH) are enzymes abundant in the central nervous system (CNS), playing important roles in neuronal energy homeostasis. Objectives: This study aimed to investigate the correlation between serum GFAP, CK, and LDH levels and depression in patients with long COVID-19 syndrome. Methods: This cross-sectional study involved 150 patients (75 males and 75 females). The Beck Depression Inventory-II (BDI-II) was used, along with standardized peripheral serum assessments. Serum GFAP, CK, and LDH levels were measured using customized direct ELISA. Data were matched by age and sex, and analyzed using Spearman non-parametric tests to assess the correlation between variables. Results: The serum level of GFAP was significantly higher in both males and females with severe depression compared to those with mild depression (282 ± 3 pg/mL, 280 ± 2.9 pg/mL, P = 0.001). The mean serum CK level was 239 ± 24.05 U/L in males and 142 ± 18.08 U/L in females (P < 0.0001). Furthermore, a significant positive correlation was found between CK serum levels and Beck scores (r = 0.33, 95% CI = 0.176 to 0.469), with a similar pattern observed for LDH (r = 0.22, 95% CI = 0.042 to 0.358). GFAP, CK, and LDH levels were higher in male patients. Conclusions: This study identified potential neurobiological mechanisms in CNS-related long COVID syndrome, suggesting that elevated astrocyte activity, along with increased serum CK and LDH levels, may contribute to the neurobiological issues seen in depressed long COVID survivors. Men appeared to be more susceptible to these changes than women. Further research is essential.

Intragenic dystrophin (DMD) duplication variant in Entlebucher Mountain Dogs with Duchenne muscular dystrophy.

Muscular dystrophies represent a group of disorders characterized by progressive muscle degeneration and weakness. An important subgroup are the dystrophin-related muscular dystrophies caused by variants in the DMD gene. They can be divided into the more severe Duchenne muscular dystrophy and the milder Becker muscular dystrophy. Here, we characterize the clinical, histopathological and molecular genetic aspects of two male Entlebucher Mountain Dogs with clinical signs of muscular dystrophy. The two dogs presented with marked dysphagia starting at the age of several weeks and in the later course recognizable exercise intolerance with highly increased serum creatine kinase levels. Histopathological signs of a dystrophic myopathy represented by degeneration of muscle fibers and signs of regeneration were present. Whole genome sequencing of one affected dog identified an intragenic 8.6 kb duplication in the X-chromosomal DMD gene, c.7528-4048_7645 + 4450dup. No other protein-changing variants in candidate genes for muscular dystrophy were identified. The duplication includes exon 52 of DMD and is predicted to lead to a frameshift and truncation of 30% of the wild-type open reading frame. Genotyping of the whole family confirmed the presence of the mutant allele in both affected dogs and the unaffected dam. The correct co-segregation of the mutant allele in the affected family as well as knowledge from humans and other species suggest the identified DMD variant as the most likely candidate variant for the muscular dystrophy phenotype in the two investigated dogs.

Genome-Wide Analysis of Exertional Rhabdomyolysis in Sickle Cell Trait Positive African Americans.

Sickle cell trait (SCT), although generally a benign carrier state of hemoglobin S (HbAS), is a risk factor for exertional rhabdomyolysis (ERM), a rare but potentially fatal consequence of highly intense physical exercise, particularly among active-duty military personnel and high-performance athletes. The association between SCT and ERM is poorly understood. The objective of this study was to elucidate the genetic basis of ERM in an SCT-positive African American cohort. SCT-positive African Americans with a personal history of ERM (cases, n = 30) and without history of ERM (controls, n = 53) were enrolled in this study. Whole-genome sequencing was performed on DNA samples isolated from peripheral white blood cells. Participants' demographic, behavioral, and medical history information was obtained. An additional 131 controls were extracted from SCT-positive subjects of African descent from the 1000 Genomes Project. SCT carriers with ERM were characterized by myotoxicity features, significant muscle involvement dominated by muscle weakness, and severe pain and substantial increase in serum creatine kinase, with a mean value of 50,480 U/L. A distinctive feature of the SCT individuals with ERM was exertional collapse, which was reported in 53.3% of the cases in the study cohort. An important factor for the development of ERM was the duration and frequency of strenuous physical activity in the cases compared to the controls. Whole-genome sequencing identified 79,696 protein-coding variants. Genome-wide association analysis revealed that the p.C477R, rs115958260 variant in the SLC44A3 gene was significantly associated with ERM event in SCT-positive African Americans. The study results suggest that a combination of vigorous exercise and a genetic predisposing factor is involved in ERM.

Challenges in The Diagnosis and Management of Idiopathic Inflammatory Myopathy: A Case Report

Background: Idiopathic inflammatory myopathy (IIM) is a group of heterogeneous disorders characterized by muscle weakness and muscle inflammation, elevated muscle enzyme, a sign of muscular inflammation, and other extra muscular manifestations. Due to how rare IIM is, as well as its lack of targeted treatments and the heterogeneity of the clinical presentation, significant challenges are posed to treatment deliveries. Case Illustration: A 30-year-old woman came with complaints of weakness in all four extremities 8 months ago accompanied by difficulty swallowing. The weakness worsened to the point where the patient had shortness of breath and a fever. Upon arrival at the hospital, the patient was in respiratory failure and intubated. Laboratory examination results showed an increase in serum creatine kinase (14.977 U/L), increased liver enzymes, and inflammatory biomarkers such as CRP and procalcitonin. Muscle biopsy results showed muscular dystrophy. Chest X-ray showed cardiomegaly with signs of pulmonary inflammation and pleural effusion. The patient received steroid therapy, cyclophosphamide, and antibiotic management for pneumonia. During treatment, the patient’s condition worsened and she was declared dead due to sepsis. Conclusion: IIM is a rare disease and has various clinical variations. Extra muscular manifestations such as pulmonary disease complicate the management of IIM.

QRS fragmentation does not predict mortality in survivors of acute myocardial infarction.

Despite advances in coronary revascularization and in heart failure management, myocardial infarction survivors remain at substantially increased mortality risk. Precise risk assessment and risk-adapted follow-up care are crucial to improve their outcomes. Recently, the fragmented QRS complex, i.e. the presence of additional spikes within the QRS complexes on a 12-lead electrocardiogram, has been discussed as a potential non-invasive risk predictor in cardiac patients. The aim of this study was to evaluate the prognostic meaning of the fragmented QRS complex in myocardial infarction survivors. 609 patients with narrow QRS complexes <120 ms were included in a prospective cohort study while hospitalized for myocardial infarction and followed for 5 years. The prevalence of the fragmented QRS complex in these patients amounted to 46.8% (285 patients). These patients had no increased hazard of all-cause death (HR 0.84, 95%-CI 0.45-1.57, p = 0.582) with a mortality rate of 6.0% compared to 7.1% in patients without QRS fragmentations. Furthermore, the risks of cardiac death (HR 1.28, 95%-CI 0.49-3.31, p = 0.613) and of non-cardiac death (HR 0.6, 95%-CI 0.26-1.43, p = 0.25) were not significantly different in patients with QRS fragmentations. However, patients with QRS fragmentations had increased serum creatine kinase concentrations (1438U/l vs. 1160U/l, p = 0.039) and reduced left ventricular ejection fractions (52% vs. 54%, p = 0.011). The hypothesis that QRS fragmentation might be a prognostic parameter in survivors of myocardial infarction was not confirmed. But those with QRS fragmentation had larger myocardial infarctions, as measured by creatine kinase and left ventricular ejection fraction.

Hexavalent chromium inhibits myogenic differentiation and induces myotube atrophy

Hexavalent chromium [Cr(VI)] is extensively used in many industrial processes. Previous studies reported that Cr(VI) exposures during early embryonic development reduced body weight with musculoskeletal malformations in rodents while exposures in adult mice increased serum creatine kinase activity, a marker of muscle damage. However, the impacts of Cr(VI) on muscle differentiation remain largely unknown. Here, we report that acute exposures to Cr(VI) in mouse C2C12 myoblasts inhibit myogenic differentiation in a dose-dependent manner. Exposure to 2 μM of Cr(VI) resulted in delayed myotube formation, as evidenced by a significant decrease in myotube formation and expression of muscle-specific markers, such as muscle creatine kinase (Mck), Myocyte enhancer factor 2 (Mef2), Myomaker (Mymk) and Myomixer (Mymx). Interestingly, exposure to 5 μM of Cr(VI) completely abolished myotube formation in differentiating C2C12 cells. Moreover, the expression of key myogenic regulatory factors (MRFs) including myoblast determination protein 1 (MyoD), myogenin (MyoG), myogenic factor 5 (Myf5), and myogenic factor 6 (Myf6) were significantly altered in Cr(VI)-treated cells. The inhibitory effect of Cr(VI) on myogenic differentiation was further confirmed in freshly isolated mouse satellite cells, a stem cell population essential for adult skeletal muscle regeneration. Furthermore, Cr(VI) exposure to fully differentiated C2C12 myotubes resulted in a decrease in myotube diameter, which was exacerbated upon co-treatment with dexamethasone. Together, our results demonstrate that Cr(VI) inhibits myogenic differentiation and induces myotube atrophy in vitro.

Effects of Tofacitinib on Muscle Remodeling in Experimental Rheumatoid Sarcopenia.

Sarcopenia is a frequent comorbidity of rheumatoid arthritis (RA). Clinical trials have shown that JAK inhibitors (JAKi) produce an asymptomatic increase in serum creatine kinase (CK) in RA, suggesting an impact on muscle. We evaluated the effect of JAKi in muscle remodeling in an experimental RA model. Antigen-induced arthritis (experimental RA, e-RA) was performed in 14 rabbits. Seven rabbits received tofacitinib (TOFA, orally 10 mg/kg/day). Animals were euthanized one day after the last ovalbumin injection, and muscles were prepared for histology, RT-PCR, and WB. C-reactive protein (CRP) and Myostatin (MSTN) serum concentration were determined by ELISA. Creatine and creatine kinase (CK) were analyzed. An increase in body weight as well as tibialis anterior cross-sectional area and diameter was observed in e-RA+TOFA vs. e-RA. e-RA decreased type II fibers and increased the myonuclei number, with all reverted by TOFA. TOFA did not modify CRP levels, neither did MSTN. TOFA significantly reduced IL-6, atrogin-1, and MuRF-1 compared with e-RA. e-RA+TOFA showed higher CK and lower creatine levels compared with e-RA. No differences in PAX-7 were found, while TOFA prevented the increase in MyoD1 in e-RA. Our model reflects the features of rheumatoid sarcopenia in RA. JAKi increased muscle mass through attenuating IL-6/JAK/STAT activation, decreasing atrogenes, and restoring muscle differentiation markers. These data together with an increase in CK support the role of CK as a valuable marker of muscle gain following JAKi treatment.

Low-intensity pulsed ultrasound alleviates doxorubicin-induced cardiotoxicity via inhibition of S100a8/a9-mediated cardiac recruitment of neutrophils.

Doxorubicin (DOX)-induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non-invasive strategies to prevent DOX-associated adverse cardiac events is urgently needed. We aimed to examine whether and how low-intensity pulsed ultrasound (LIPUS) plays a protective role in DOX-induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX-induced cardiomyopathy. Non-invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA-seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR-238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX-induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX-induced cardiac oxidative stress and fibrosis. RNA-seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX-LIPUS and DOX-Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX-induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR-238901 showed a similar heart protective effect against DOX-induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX-induced cardiotoxicity through inhibition of S100a8/a9-mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.

Immune-Mediated Necrotizing Myopathy(IMNM)

Immune-mediated necrotizing myopathy (IMNM) has recently been classified from polymyositis, and it clinically shows subacute progressive proximal dominant muscle weakness. Laboratory examinations show a great increase in serum creatine kinase and prominent necrotic muscle fibers without any pathological invasion of inflammatory cells. It is thought to be an autoimmune disease because SRP and HMGCR antibodies have been detected in many cases. These two antibodies affect the pathophysiology of IMNM. Immuno-modulating therapies have usually been induced. Moreover, intensive treatments are necessary in cases of corticosteroid resistant IMNM.

Limb girdle muscular dystrophy 23 caused by compound heterozygous mutations of LAMA2 gene.

Mutations of LAMA2 gene are associated with congenital muscular dystrophy (CMD). The LAMA2-related CMD mainly consists of two diseases, merosin deficient congenital muscular dystrophies type 1A (MDC1A) and limb girdle muscular dystrophy 23 (LGMD23). LGMD23 is characterized by slowly progressive proximal muscle weakness, which primarily affects the lower limbs and results in gait difficulties. Additional clinical features include increased serum creatine kinase, abnormal electromyography with or without white matter abnormalities on brain imaging. Clinical data were collected from a Chinese Han family. Whole-exome sequencing, Sanger sequencing, RT-PCR and TA clone sequencing were performed on the family members. Compound heterozygous mutations of LAMA2: c.1693C > T (p. Q565*) (maternally inherited) and c.9212-6T > G (paternally inherited) were identified and confirmed in the proband. The mutation c.1693C > T (p. Q565*) was classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. By performing RT-PCR and TA clone sequencing, an insertion of 40-bp intronic sequence (intron 64) was found in the transcripts of the proband and her father, which resulted in a frameshift and premature truncation codon of the LAMA2. In particular, the variant truncated the LamG domain of the LAMA2. Therefore, the c.9212-6T>G was classified as likely pathogenic according to American College of Medical Genetics and Genomics (ACMG) guidelines. Our findings described two novel mutations in a girl with LGMDR23, which contributes to the genetic counseling of the family and expands the clinical and molecular spectrums of the rare disease.

Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment.

Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported. Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. Sanger sequencing was used to validate the variants identified in the siblings and their parents. In vitro functional study was performed. Results: A homozygous mutation, c.197G>A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. However, the actual genotype-phenotype relationship needs more study. Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity.

The liver and blood cells are responsible for creatine kinase clearance in blood Circulation: A retrospective study among different human diseases

BackgroundMuscle damage leads to increased serum creatine kinase (CK) levels in diseases such as acute myocardial infarction. Still, many individuals have abnormal serum CK activities lacking muscle-related diagnoses. The current study hypothesized that failed or overactivated CK clearance by non-muscle organs/tissues might be responsible for increased or decreased CK activities in blood. MethodsWe analyzing 37,081 independent CK test results in 36 human diseases during the past 5 y. ResultsWe found that 33 out of 36 diseases were associated with decreased median CK activities compared to healthy controls. Besides muscle damage-related conditions, the highest mean CK activities were observed in hepatitis and cirrhosis. In contrast, 6 blood cell-related illnesses had the lowest mean CK values. ROC analysis showed that CK activities were the best biomarkers (AUC: 0.80–0.94) for the 6 blood-related diseases, especially myeloproliferative disorders. The principal component analysis revealed that the same category of diseases, such as liver-, blood -, kidney-, cancers, and vascular-related diseases, had clustered CK distributions. ConclusionsWe proposed that the liver and blood cells were mainly responsible for CK clearance in blood circulation based on overall results. The testable mechanisms were presented and discussed.

Severe unilateral nephrolithiasis and recurrent colic in a horse

AbstractUrolithiasis is an uncommon disorder reported in horses. Calculi located in the kidneys and ureters are often underdiagnosed. Associated clinical signs include weight loss, anorexia, haematuria, dysuria, colic and polyuria/polydipsia. A 26‐year‐old Thoroughbred gelding was referred for evaluation of an acute colic episode of 5‐hour duration. Haematologic analysis revealed increased serum creatine kinase and creatinine concentrations. Abdominocentesis yielded serosanguineous, mildly cloudy fluid with a lactate of 9.6 mmol/L (&lt;2 mmol/L). Exploratory laparotomy was recommended. Surgical intervention was declined, and the horse was humanely euthanased. Limited postmortem evaluation was performed. A 3.633 kg nephrolith measuring 23.6 × 16.2 × 8.9 cm was completely effacing the left kidney. Crystallography and infrared spectroscopy (attenuated total reflection and Fourier transform infrared) revealed a 100% calcium carbonate nephrolith. Carbonate calcium calculi are the most common subtype in horses. Nephrolithiasis should be considered as a differential diagnosis for colic and haematologic evidence of azotaemia in horses.

Rhabdomyolysis in a male adolescent associated with monotherapy of fluvoxamine

Rhabdomyolysis is a syndrome resulting from striated muscular breakdown, which may occur due to drug therapy with agents such as selective serotonin reuptake inhibitors (SSRIs). Although studies have shown that...

EFFECT OF BOMA CONFINEMENT ON HEMATOLOGIC AND BIOCHEMICAL VALUES IN FREE-RANGING WHITE RHINOCEROS (CERATOTHERIUM SIMUM) IN KRUGER NATIONAL PARK, SOUTH AFRICA.

Boma adaptation is an important component of rhinoceros translocations to allow transition to new diets, restricted space, and quarantine for disease screening. However, up to 20% of recently captured white rhinoceros (Ceratotherium simum) do not adjust to captivity, resulting in early release or even death. The causes and physiologic consequences of maladaptation to boma confinement are poorly understood. The aim of this investigation was to evaluate hematologic and serum biochemical changes in maladapted rhinoceros compared to animals that adapted under the same boma conditions. Ninety-six white rhinoceros were captured between 2009 and 2011 in Kruger National Park, South Africa and placed in bomas prior to translocation. Weight, complete blood count, and serum biochemical panel results were recorded when rhinoceros were placed in the boma and repeated on the day of release. In this study, the mean duration of boma confinement for maladapted white rhinoceros was 13 d (range 8-16 d) compared to 89.9 d (range 39-187 d) for adapted animals. Mean weight loss between capture and release was significantly greater in maladapted rhinoceros (224.0 versus 65.9 kgs; P<0.001). Although adapted rhinoceros had statistically significant changes in some hematologic and biochemical values, most were not considered clinically relevant. In contrast, the maladapted rhinoceros had significant changes at the time of early release from the boma, including evidence of leukocytosis with left shift, lymphopenia, eosinopenia, decreased red blood cell count and hematocrit, increased serum creatine kinase, and decreased serum calcium, phosphorus, and magnesium values. Along with loss of body condition, these findings were consistent with a stress-associated catabolic response. These changes occurred in the first 2 wk of confinement, and the results provide a foundation for evaluating adaptation in white rhinoceros. Future studies should focus on factors that improve adaptation and welfare of recently confined free-ranging white rhinoceros.

Resveratrol alleviated 5-FU-induced cardiotoxicity by attenuating GPX4 dependent ferroptosis

The clinical use of 5-fluorouracil (5-FU), a potent antitumor agent, was limited by severe cardiotoxic effects. The present study was aimed to investigate the protective effects of resveratrol (Res) on 5-FU-induced cardiotoxicity and to explore its potential mechanisms.The cardiotoxicity model was intraperitoneal injection of 5-FU at the dose of 30 mg/kg for 7 consecutive days. Plasma enzymes activities, cardiac tissues were assessed after treatment with Res for 3 weeks. Ferrostatin-1 (Fer-1) was used as ferroptosis inhibitor. In H9c2 cardiomyocyte cells, cell viability, generation of reactive oxygen species (ROS), mitochondrial activity and cellular Fe2+ levels were measured. Western-blot assay was performed to evaluate the protein level of ferroptosis in vitro and in vivo. In the mice model, Res reduced 5-FU-induced cardiomyocyte injury (ferroptosis, myofibrillar loss and vacuolization). In addition, increased serum creatine kinase (CK), lactate dehydrogenase (LDH), malonaldehyde (MDA) and Fe2+ activity and decreased activities of glutathione (GSH) were observed in 5-FU group. These changes were prevented by treatment with Res. In H9c2 cardiomyocyte cells, Res increased the cell viability and attenuated cell ferroptosis as measured by DCFH-DA, TMRE and Calcein AM staining. In addition, 5-FU induced a reduction in GPX4, FTH1, Nrf2 and NQO1 and activation of TfR and P53 compared with the control group. However, Res effectively inhibited the changes in ferroptosis associated proteins in vitro and in vivo. Res possessed the cardioprotective potential against 5-FU induced cardiotoxicity. Moreover, Res attenuates 5-FU-induced cardiotoxicity via inhibiting GPX4 dependent ferroptosis.

VP.09 Clinical characteristics and gene analysis of 10 rare cases with coexistence of double genetic diseases

Coexistence of double genetic diseases in one patient is quite rare. In this study, we aimed to analyse the clinical and genetic characteristics of patients with double genetic diseases. Clinical and genetical data of patients with double genetic diseases from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed. Among these 10 children, 7 were boys and 3 were girls, with last follow-up ages ranging from 2.0 to 7.9 years old. Cases 1-5, all boys, showed myopathic gait, poor running and jumping, and significantly increased serum creatine kinase level, as well as pathogenic variations in DMD gene, and were diagnosed as DMD/BMD. However, all of them had other symptoms and signs that were inconsistent with DMD/BMD. Further trio-based whole exome sequencing was performed. The 5 patients also had a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, Phelmn-McDerimid syndrome and intracranial cavernous hemangioma. The remaining five cases had complicated clinical manifestations, or disease development that could not be explained by the first diagnosed disease. Type IX collagen gene related disease, and neurofibromatosis type 1 were identified in case 6. Collagen VI-related myopathy with and osteogenesis imperfecta type XV was identified in case 7. Turner syndrome with chromosome karyotype of 45,X, and Segawa syndrome were identified in case 8. Chromosome 22q11.2 microduplication syndrome with a 2.64Mb microduplication, and autosomal dominant lower extremity-predominant spinal muscular atrophy-1 caused by <i>DYNC1H1</i> gene mutation were confirmed in case 9. KBG syndrome due to <i>ANKRD11</i> gene mutation, and neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy caused by <i>IRF2BPL</i> gene mutation were identified in case 10. We found between the two pathogenic genes, either or both of them were <i>de novo</i> mutations. The clinical manifestations of patients with double genetic diseases were complex and diverse. Whole exome sequencing of the core pedigree combining with a variety of molecular genetic tests would be helpful for accurate diagnosis, genetic counseling and individualized management. This study provides important information and basis for the diagnosis of patients with coexistence of double genetic diseases.

Case report: One child with an autism spectrum disorder who had chronically elevated serum levels of CK and CK-MB

Some patients with autism spectrum disorder (ASD) exhibit elevated serum creatine kinase levels, which are believed to be associated with mitochondrial dysfunction. Although a few articles have reported this situation in the past and the increase mostly ranges from 100 to 300 U/L, there is a paucity of previous study focusing on the serum creatine kinase MB isoenzyme. This article discusses a 5-year-old girl with ASD, whose serum creatine kinase and creatine kinase MB isoenzyme have been rising for nearly 2 years, fluctuating at 584–993 and 111–625 U/L respectively. Except for behavioral and language symptoms associated with ASD, the child appears normal in other aspects. The child's laboratory tests showed no abnormality, except that the serum levels of lactic acid was slightly higher than normal (1.89 mmol/L, normal 1.33–1.78 mmol/L). The child was prescribed with a traditional Chinese medicine during the process and the serum creatine kinase MB isoenzyme level decreased dramatically to 111 U/L after the treatment. This study firstly recorded the serum creatine kinase levels and the MB isoenzyme in patients with autism spectrum disorder for nearly 2 years, indicating that patients with ASD may experience long-term increases in serum creatine kinase and creatine kinase MB isoenzyme, and that the traditional Chinese medicine decoction Xinfukang can temporarily reduce the serum creatine kinase MB isoenzyme level in patients. Nevertheless, the effect is not sustained. Therefore, it is of great importance to conduct long-term longitudinal studies so as to elucidate the potential mechanism responsible for long-term elevation of serum creatine kinase level.

Clinical characteristics of 68 children with atypical hand, foot, and mouth disease caused by coxsackievirus A6: a single-center retrospective analysis.

BackgroundHand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CV-A6) has become prevalent in many parts of the world. It is commonly referred to as atypical HFMD which more likely to present as bullous lesions. Compared with traditional HFMD, its misdiagnosis rate is relatively high, which brings difficulties to clinical diagnosis. We retrospectively analyze the clinical characteristics of children with HFMD with bullous lesions caused by CV-A6.MethodsThe study included 68 children with atypical HFMD caused by CV-A6 who were hospitalized from 2018 to 2020. Data of the children including age, sex, month of HFMD onset, the morphologies and distribution of rashes, the details of fever, the presence or absence of onychomadesis, and laboratory test results were analyzed and compared between an infant group (<1 year), a toddler group (1–<3 years), and a preschool group (3–<6 years).ResultsOf the 68 children, 67 were younger than 5 years old, with a male to female ratio of 1.62:1. The disease peaked in the period from June to September. With 75.0% of the infant group had more than three kinds of rashes; 95.0% of the preschool group had rashes in more than five locations. These differences were statistically significant (P<0.05). All children had fever. The peak fever in the toddler group was lower (P=0.033). No critical cases were observed in any of the groups. Of the 61 children who were successfully followed up, 68.9% developed onychomadesis within 2–3 weeks. The proportion of cases with abnormal liver function was 83.3%, 41.7%, and 10.0% in the infant, toddler, and preschool groups (P<0.001). The proportion of cases with increased serum creatine kinase MB isoenzyme (CK-MB) were significantly higher in the toddler group (P<0.05).ConclusionsAtypical HFMD caused by CV-A6 infection usually occurred in children under 5 years old. The morphologies of the rashes in the infant group changed more, while the rashes in the preschool group was more widely distributed. The incidence of critical cases was low. More than half of the cases can develop onychomadesis in the recovery period. Organ damage was relatively mild in the preschool group.

2-Aminoethoxydiphenyl-borate reduces arsenic-induced cardiotoxicity in rats.

Objective To study the effect of 2-Aminoethoxydiphenyl-borate (2-APB) on arsenic-induced cardiotoxicity. Methods 32 male Specific Pathogen Free (SPF) grade Sprague Dawley (SD) rats are randomly divided into 4 groups: control group, natural recovery group after arsenic poisoning (sodium arsenite, NaAsO2 group), low dose 2-APB treatment group after arsenic poisoning (L-2-APB group) and high dose 2-APB treatment group after arsenic poisoning (H-2-APB group) (n = 8 per group). After establishing the rat model, all rats are examined by echocardiography to obtain global longitudinal strain (GLS) parameters. Then, all rats are killed to obtain serum and heart samples. The morphological changes of cardiomyocytes are observed by hematoxylin-eosin (HE) staining. And the levels of serum markers of myocardial injury and the indexes related to oxidative stress and apoptosis are measured. Results In this study, compared with the control group, the NaAsO2 group has decreased absolute value of GLS, Superoxide dismutase (SOD), Glutathione peroxidase (GSH-px) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity, and Bcl-2 levels, increased serum Creatine Kinase Myocardial Band (CKMB), serum Lactate Dehydrogenase (LDH), Malonic dialdehyde (MDA) and cleaved caspase-3 activity, and Bax levels (P＜0.05). Furthermore, 2-APB led to dose-dependent increase in absolute values of GLS-endo and GLS-mid, SOD, GSH-px and SERCA activity, and Bcl-2 levels, decrease serum CKMB and LDH, MDA and cleaved caspase-3 activity, and Bax levels compared with the NaAsO2 group (P＜0.05). Conclusion 2-APB can reduce the degree of arsenic-induced cardiotoxicity.