The utility of electrodiagnostic testing in unprovoked rhabdomyolysis in the era of next-generation sequencing.

INTRODUCTION/AIMS: Rhabdomyolysis is an etiologically heterogeneous, acute necrosis of myofibers characterized by transient marked creatine kinase (CK) elevation associated with myalgia, muscle edema, and/or weakness. The study aimed to determine the role of electrodiagnostic (EDX) testing relative to genetic testing and muscle biopsy in patients with unprovoked rhabdomyolysis in identifying an underlying myopathy. METHODS: EDX database was reviewed to identify unprovoked rhabdomyolysis patients who underwent EDX testing between January 2012 and January 2022. Each patient's clinical profile, EDX findings, muscle pathology, laboratory, and genetic testing results were analyzed. RESULTS: Of 66 patients identified, 32 had myopathic electromyography (EMG). Muscle biopsy and genetic testing were performed in 41 and 37 patients, respectively. A definitive diagnosis was achieved in 15 patients (11 myopathic EMG and 4 nonmyopathic EMG; p = .04) based on abnormal muscle biopsy (4/11 patients) or genetic testing (12/12 patients, encompassing 5 patients with normal muscle biopsy and 3 patients with nonmyopathic EMG). These included seven metabolic and eight nonmetabolic myopathies (five muscular dystrophies and three ryanodine receptor 1 [RYR1]-myopathies). Patients were more likely to have baseline weakness (p < .01), elevated baseline CK (p < .01), and nonmetabolic myopathies (p = .03) when myopathic EMG was identified. DISCUSSION: Myopathic EMG occurred in approximately half of patients with unprovoked rhabdomyolysis, more likely in patients with weakness and elevated CK at baseline. Although patients with myopathic EMG were more likely to have nonmetabolic myopathies, nonmyopathic EMG did not exclude myopathy, and genetic testing was primarily helpful to identify an underlying myopathy. Genetic testing should likely be first-tier diagnostic testing following unprovoked rhabdomyolysis.

Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

Rhabdomyolysis in older adults: outcomes and prognostic factors.

BACKGROUND: Rhabdomyolysis is a common condition in older adults, often associated with falls. However, prognostic factors for rhabdomyolysis have mainly been studied in middle-aged populations. OBJECTIVE: To test the hypothesis that age influences rhabdomyolysis prognostic factors. METHODS: This retrospective single-center observational study included all patients with a creatine kinase (CK) level greater than five times normal, admitted to Rennes University Hospital between 2013 and 2019. The primary endpoint was 30-day in-hospital mortality rate. RESULTS: 343 patients were included (median age: 75 years). The mean peak CK was 21,825 IU/L. Acute renal failure occurred in 57.7% of the cases. For patients aged 70 years and over, the main etiology was prolonged immobilization after a fall. The 30-day in-hospital mortality rate was 10.5% (23 deaths). The Charlson score, number of medications and CK and creatinine levels varied according to age. Multivariate analysis showed age to be a factor that was associated, although not proportionally, with 30-day in-hospital mortality. CONCLUSION: Factors influencing rhabdomyolysis severity were not randomly distributed according to age. The term rhabdomyolysis encompasses various clinical realities and is associated with different mechanisms. More research is needed to better understand the physio-pathological and prognostic factors of rhabdomyolysis, especially in older adults.

Α rare case of myopathy, lactic acidosis, and severe rhabdomyolysis, due to a homozygous mutation of the ferredoxin-2 (FDX2) gene.

Mitochondrial myopathy is a severe metabolic myopathy related to nuclear or mitochondrial DNA dysfunction. We present a rare case of mitochondrial myopathy, presented with multiple episodes of proximal muscle weakness, lactic acidosis, and severe rhabdomyolysis (CPK 319,990 U/L, lactic acid 22.31 mmol/L, and GFR 3.82 mL/min/1.73m2 ). She was hospitalized in the pediatric intensive care unit due to acute kidney injury, elevated blood pressure, and deterioration of respiratory and cardiac function. Investigation for inherited metabolic disorders showed elevated levels of ammonia, lactic acid to pyruvic acid ratio, and urine ketone bodies. Exome sequencing detected a homozygous pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) and a heterozygous variant of uncertain significance in MSTO1 (ENST00000538143:p.Leu137Pro/c.410 T > C). After Sanger sequencing, the p.Met4Leu pathogenic variant in FDX2 (ENST00000541276:p.Met4Leu/c.10A > T) was identified in a heterozygous state in both her parents and sister. Recently, pathogenic variants in the FDX2 gene have been associated with mitochondrial myopathy, lactic acidosis, optic atrophy, and leukoencephalopathy. Only four reports of FDX2-related rhabdomyolysis have been described before, but none of the previous patients had hyperammonemia. This is a rare case of severe mitochondrial myopathy in a pediatric patient related to a pathogenic FDX2 variant, suggesting the need for genetic analysis of the FDX2 gene in cases of suspicion of mitochondrial myopathies.

Safety monitoring of drug-induced muscle injury and rhabdomyolysis: a biomarker-guided approach for clinical practice and drug trials.

Skeletal muscle tissue (SKM) may be damaged due to mechanical, metabolic, and exertional causes. However, drug-induced myopathy is among the most frequent causes of muscle disease. The clinical picture of drug-induced myopathies may be highly variable. It may present as asymptomatic or mild myalgias, with or without muscle weakness, which are likely underreported. However, it may also appear as chronic myopathy with severe weakness and, rarely, even as massive rhabdomyolysis with acute kidney injury (AKI). Unfortunately, the available biomarkers for SKM injury do not fully meet the needs for satisfactory detection of drug-induced damage, both in clinical and research settings, mainly due to their low sensitivity and specificity. Therefore, the present study proposes a strategy for drug safety monitoring using the available biomarkers of SKM injury. Moreover, we will discuss mechanisms of drug-induced SKM injury, traditional laboratory testing for SKM injury, and novel skeletal myocyte biomarkers under investigation. This can be incredibly useful in both clinical practice and for de-challenge/re-challenge investigational trials where the risk of drug-induced SKM injury is present.

Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.

Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis. Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents. This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.

Study of the Relationship Between Liver Function Markers and Traumatic Rhabdomyolysis: A Retrospective Study of Hemorrhagic Patients Admitted to Intensive Care Unit in a Level I Trauma Center.

BACKGROUND: Traumatic rhabdomyolysis (RM) is common and contributes to the development of medical complications, of which acute renal failure is the best described. Some authors have described an association between elevated aminotransferases and RM, suggesting the possibility of associated liver damage. Our study aims to evaluate the relationship between liver function and RM in hemorrhagic trauma patients. METHODS: This is a retrospective observational study conducted in a level 1 trauma center analyzing 272 severely injured patients transfused within 24 hours and admitted to intensive care unit (ICU) from January 2015 to June 2021. Patients with significant direct liver injury (abdominal Abbreviated Injury Score [AIS] >3) were excluded. Clinical and laboratory data were reviewed, and groups were stratified according to the presence of intense RM (creatine kinase [CK] >5000 U/L). Liver failure was defined by a prothrombin time (PT)-ratio <50% and an alanine transferase (ALT) >500 U/L simultaneously. Correlation analysis was performed using Pearson's or Spearman's coefficient depending on the distribution after log transformation to evaluate the association between serum CK and biological markers of hepatic function. Risk factors for the development of liver failure were defined with a stepwise logistic regression analysis of all relevant explanatory factors significantly associated with the bivariate analysis. RESULTS: RM (CK >1000 U/L) was highly prevalent in the global cohort (58.1%), and 55 (23.2%) patients presented with intense RM. We found a significant positive correlation between RM biomarkers (CK and myoglobin) and liver biomarkers (aspartate transferase [AST], ALT, and bilirubin). Log-CK was positively correlated with log-AST (r = 0.625, P < .001) and log-ALT (r = 0.507, P < .001) and minimally with log-bilirubin (r = 0.262, P < .001). Intensive care unit stays were longer for intense RM patients (7 [4-18] days vs 4 [2-11] days, P < .001). These patients required increased renal replacement therapy use (4.1% vs 20.0%, P < .001) and transfusion requirements. Liver failure was more common (4.6% vs 18.2%, P < .001) for intense RM patients. It was associated with bivariate and multivariable analysis with intense RM (odds ratio [OR], 4.51 [1.11-19.2]; P = .034), need for renal replacement therapy, and Sepsis-Related Organ Failure Assessment Score (SOFA) score on day 1. CONCLUSIONS: Our study established the presence of an association between trauma-related RM and classical hepatic biomarkers. Liver failure was associated with the presence of intense RM in bivariate and multivariable analysis. Traumatic RM could have a role in the development of other system failures, specifically at the hepatic level, in addition to the already known and well-described renal failure.

Oral Dantrolene for Myopathic Symptoms in Malignant Hyperthermia-Susceptible Patients: A 25-Year Retrospective Cohort Study of Adverse Effects and Tolerability.

BACKGROUND: Patients susceptible to malignant hyperthermia (MH) may experience disabling manifestations of an unspecified myopathy outside the context of anesthesia, including myalgia, fatigue, or episodic rhabdomyolysis. Clinical observations suggest that oral dantrolene may relief myopathic symptoms in MH-susceptible (MHS) patients. However, high-dose oral dantrolene has been associated with severe hepatotoxicity. METHODS: In a retrospective database review (1994-2018), we investigated a cohort of patients who were diagnosed as MHS by a positive caffeine-halothane contracture test (CHCT), had myopathic manifestations, and received oral dantrolene. Our aim was to investigate the occurrence of serious adverse effects and the adherence to oral dantrolene therapy. We also explored factors associated with self-reported clinical improvement, considering as nonresponders patients with intolerable adverse effects or who reported no improvement 8 weeks after starting treatment. RESULTS: Among 476 MHS patients with positive CHCT, 193 had muscle symptoms, 164 started oral dantrolene, 27 refused treatment, and 2 were excluded due to abnormal liver function before starting therapy. There were no serious adverse effects reported. Forty-six of 164 patients (28%; 95% confidence interval [CI], 22%-35%) experienced mild to moderate adverse effects. Twenty-two patients (22/164, 13%; 95% CI, 9%-19%) discontinued treatment, among which 16 due to adverse effects and 6 due to lack of improvement. One hundred forty-two patients (87%; 95% CI, 80%-90%) adhered to therapy and reported improvement of myalgia (n = 78), fatigue (n = 32), or rhabdomyolysis/hiperCKemia (n = 32). The proportion of responders was larger among patients with MH history than among those referred due to a clinical myopathy with nonpertinent anesthetic history (97% vs 79%, respectively; 95% CI of the difference, 8.5-28; P < .001). Patients with a sarcoplasmic reticulum Ca2+ release channel ryanodine receptor gene ( RYR1 ) variant had higher odds of responding to dantrolene treatment (OR, 6.4; 95% CI, 1.3-30.9; P = .013). Dantrolene median dose was 50 (25-400) and 200 (25-400) mg·day -1 in responders and nonresponders, respectively. CONCLUSIONS: We found that oral dantrolene produced no serious adverse effects within the reported dose range, and was well tolerated by most MH-susceptible patients presenting myopathic symptoms. Our study provides dosing and adverse effect data as a basis for further randomized controlled clinical trials to determine the efficacy of oral dantrolene for symptomatic relief in MHS-related myopathies.

Levofloxacin-induced acute rhabdomyolysis: A case report.

Quinolones can cause rhabdomyolysis, but rhabdomyolysis secondary to quinolone use is uncommon, and few reports associate rhabdomyolysis with levofloxacin use. We report a case of acute rhabdomyolysis associated with levofloxacin use. A 58-year-old Chinese woman developed myalgia and difficulty walking ~ 4 days after taking levofloxacin for a respiratory infection. Blood biochemistry revealed elevated peripheral creatine kinase and liver enzyme levels, but the patient did not develop an acute kidney injury. Her symptoms resolved after discontinuation of levofloxacin. This case report highlights the need for monitoring of blood biochemistry in patients taking levofloxacin to enable early diagnosis and treatment of potentially life-threatening myositis.

Crush injury and syndrome: A review for emergency clinicians.

INTRODUCTION: Primary disasters may result in mass casualty events with serious injuries, including crush injury and crush syndrome. OBJECTIVE: This narrative review provides a focused overview of crush injury and crush syndrome for emergency clinicians. DISCUSSION: Millions of people worldwide annually face natural or human-made disasters, which may lead to mass casualty events and severe medical issues including crush injury and syndrome. Crush injury is due to direct physical trauma and compression of the human body, most commonly involving the lower extremities. It may result in asphyxia, severe orthopedic injury, compartment syndrome, hypotension, and organ injury (including acute kidney injury). Crush syndrome is the systemic manifestation of severe, traumatic muscle injury. Emergency clinicians are at the forefront of the evaluation and treatment of these patients. Care at the incident scene is essential and focuses on treating life-threatening injuries, extrication, triage, fluid resuscitation, and transport. Care at the healthcare facility includes initial stabilization and trauma evaluation as well as treatment of any complication (e.g., compartment syndrome, hyperkalemia, rhabdomyolysis, acute kidney injury). CONCLUSIONS: Crush injury and crush syndrome are common in natural and human-made disasters. Emergency clinicians must understand the pathophysiology, evaluation, and management of these conditions to optimize patient care.

Gitelman syndrome with Graves' disease leading to rhabdomyolysis: a case report and literature review.

A 14-year-old male patient who suffered from limb numbness, fatigue, and hypokalemia was considered Graves' disease (GD) complicated with thyrotoxic periodic paralysis (TPP) at the first diagnosis. Although with the treatment of antithyroid drugs, he developed severe hypokalemia and rhabdomyolysis (RM). Further laboratory tests revealed hypomagnesemia, hypocalciuria, metabolic alkalosis, hyperrenin, and hyperaldosteronemia. Genetic testing revealed compound heterozygous mutations in the SLC12A3 gene (c.506-1G > A, c.1456G > A) encoding the thiazide-sensitive sodium-chloride cotransporter, which presented a definitive diagnosis of Gitelman syndrome (GS). Moreover, gene analysis revealed his mother diagnosed with subclinical hypothyroidism due to Hashimoto's thyroiditis carried the c.506-1G > A heterozygous mutation in the SLC12A3 gene and his father carried the c.1456G > A heterozygous mutation in the SLC12A3 gene. His younger sister who had hypokalemia and hypomagnesemia carried the same compound heterozygous mutations as the proband and was diagnosed with GS as well, but with a much milder clinical presentation and better treatment outcome. This case suggested the potential relationship between GS and GD, clinicians should strengthen the differential diagnosis to avoid missed diagnosis.

Paediatric rhabdomyolysis: A UK centre's 10-year retrospective experience.

AIMS: To describe the aetiologies of paediatric rhabdomyolysis and explore the medium-term renal consequences. METHODS: Retrospective, single-centre review of children with rhabdomyolysis. RESULTS: Two hundred and thirty-two children met inclusion criteria for the analysis. Mean age at presentation was 8.4 (SD ± 5.5) years. The commonest aetiology was infection (28%), with viral myositis making up the clear majority (75%). Trauma was identified as a cause in 18% of children, seizures in 10% and immune-mediated mechanisms in 8%. Acute kidney injury (AKI) was present in 32% of the cases overall. Children with AKI tended to be younger, with higher peak creatine kinase (CK) and active urinary sediment on urinalysis at presentation. AKI and the need for renal replacement therapy (RRT) were associated with a prolonged hospital stay (15 (interquartile range, IQR 6.5-33) vs. 2 (IQR 0-7) days). A total of 18 children and young people required RRT, with a mean duration of 7.1 ± 4.3 days. Those who received RRT were more likely to have abnormalities on urinalysis at presentation (46% vs. 5%). Over the period of the study, 9% of children died and 2% met criteria for a diagnosis of chronic kidney disease. CONCLUSIONS: This large paediatric rhabdomyolysis case series provides new and unique insights into the condition. Our results highlight the common aetiologies and provide evidence of good renal recovery overall, even in the most severely affected cases. Abnormalities of urinalysis appear to be important in predicting the development of AKI and the need for RRT.

[Diagnostic approach to rhabdomyolysis]. / Vignette diagnostique de l'étudiant. Approche diagnostique de la rhabdomyolyse.

Rhabdomyolysis is a clinical syndrome related to the damage of skeletal muscle. The symptomatology is often poor, but it classically includes muscle weakness, myalgia and red-brown urine. The causes may be multiple but are most frequently traumatic : the so-called "crush syndrome". The diagnosis is based on the increase in serum creatine kinase, which is sometimes associated with myoglobinuria. Rhabdomyolysis may cause severe complications, such as ionic disorders or acute kidney injury which can lead to the death of the patient.

La rhabdomyolyse est un syndrome clinique lié à la destruction du muscle squelettique. La symptomatologie est souvent pauvre et associe classiquement une faiblesse musculaire, des myalgies et des urines noirâtres. Les causes peuvent être multiples, mais sont le plus fréquemment traumatiques et regroupées sous le terme anglophone de «crush syndrome¼. Le diagnostic repose sur la majoration sérique de la créatine kinase, à laquelle s'associe parfois une myoglobinurie. Rarement bénigne, la rhabdomyolyse peut engendrer des complications sévères, telles que des troubles ioniques ou une insuffisance rénale pouvant mener au décès du patient.

Recent advances in our understanding of genetic rhabdomyolysis.

PURPOSE OF REVIEW: This review summarizes recent advances in our understanding of the genetics of rhabdomyolysis. RECENT FINDINGS: Rhabdomyolysis is the acute breakdown of myofibres resulting in systemic changes that can be life-threatening. Environmental triggers, including trauma, exercise, toxins and infections, and/or gene defects can precipitate rhabdomyolysis. A schema (aptly titled RHABDO) has been suggested for evaluating whether a patient with rhabdomyolysis is likely to harbour an underlying genetic defect. It is becoming increasingly recognized that defects in muscular dystrophy and myopathy genes can trigger rhabdomyolysis, even as the sole or presenting feature. Variants in genes not previously associated with human disease have been identified recently as causative of rhabdomyolysis, MLIP , MYH1 and OBSCN . Our understanding of the pathomechanisms contributing to rhabdomyolysis have also improved with an increased awareness of the role of mitochondrial dysfunction in LPIN1 , FDX2 , ISCU and TANGO2 -mediated disease. SUMMARY: An accurate genetic diagnosis is important for optimal clinical management of the patient, avoiding associated triggers and genetic counselling and cascade screening. Despite recent advances in our understanding of the genetics contributing to rhabdomyolysis, many patients remain without an accurate genetic diagnosis, suggesting there are many more causative genes, variants and disease mechanisms to uncover.

Variable clinical severity in TANGO2 deficiency: Case series and literature review.

Biallelic pathogenic variants in the TANGO2 (transport and Golgi organization 2 homolog) gene have been identified as causing a rare metabolic disorder characterized by susceptibility to recurrent rhabdomyolysis, lactic acidosis, encephalopathy, and life-threatening tachyarrhythmias. Recently published reports suggest variable clinical severity and phenotypes. This study details five new patients from two families with biallelic pathogenic variants in the TANGO2 gene identified by whole exome sequencing and includes the largest number of affected individuals from a single family reported to date. We document significant intrafamilial variability and highlight that milder phenotypes may be underrecognized. We present biochemical and clinical data to help highlight the features that aid in consideration of this condition in the differential with disorders of fatty acid oxidation. We also present a comprehensive literature review summarizing the molecular, clinical, and biochemical findings for 92 individuals across 13 publications. Of the 27 pathogenic variants reported to date, the recurrent exons 3-9 deletion represents the most common variant seen in 42% of individuals with TANGO2 deficiency. Common clinical features seen in >70% of all individuals include acute metabolic crisis, rhabdomyolysis, neurologic abnormalities, developmental delay, and intellectual disability. Findings such as elevated creatine kinase, hypothyroidism, ketotic hypoglycemia, QT prolongation, or abnormalities of long-chain acylcarnitines and urine dicarboxylic acids should raise clinical suspicion for this life-threatening condition.

Rhabdomyolysis Caused by Hypothyroidism: Research Progress.

Rhabdomyolysis (RM) refers to the clinical syndrome caused by the release of intracellular substances into the extracellular fluid and blood circulation after rhabdomyocyte destruction due to various etiologies. In severe cases, RM can lead to life-threatening conditions such as acute kidney injury. Hypothyroidism is a rare cause of RM that can lead to missed diagnosis or misdiagnosis, and the condition worsens in the absence of timely and effective treatment. Herein, reported cases of RM caused by hypothyroidism are summarized, and clinical diagnosis and treatment recommendations are proposed to facilitate early identification and treatment of the disease.

Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is included in many newborn screening (NBS) programs. Acylcarnitine-based NBS for LCHADD not only identifies LCHADD, but also the other deficiencies of the mitochondrial trifunctional protein (MTP), a multi-enzyme complex involved in long-chain fatty acid ß-oxidation. Besides LCHAD, MTP harbors two additional enzyme activities: long-chain enoyl-CoA hydratase (LCEH) and long-chain ketoacyl-CoA thiolase (LCKAT). Deficiency of one or more MTP activities causes generalized MTP deficiency (MTPD), LCHADD, LCEH deficiency (not yet reported), or LCKAT deficiency (LCKATD). To gain insight in the outcomes of MTP-deficient patients diagnosed after the introduction of NBS for LCHADD in the Netherlands, a retrospective evaluation of genetic, biochemical, and clinical characteristics of MTP-deficient patients, identified since 2007, was carried out. Thirteen patients were identified: seven with LCHADD, five with MTPD, and one with LCKATD. All LCHADD patients (one missed by NBS, clinical diagnosis) and one MTPD patient (clinical diagnosis) were alive. Four MTPD patients and one LCKATD patient developed cardiomyopathy and died within 1 month and 13 months of life, respectively. Surviving patients did not develop symptomatic hypoglycemia, but experienced reversible cardiomyopathy and rhabdomyolysis. Five LCHADD patients developed subclinical neuropathy and/or retinopathy. In conclusion, patient outcomes were highly variable, stressing the need for accurate classification of and discrimination between the MTP deficiencies to improve insight in the yield of NBS for LCHADD. NBS allowed the prevention of symptomatic hypoglycemia, but current treatment options failed to treat cardiomyopathy and prevent long-term complications. Moreover, milder patients, who might benefit from NBS, were missed due to normal acylcarnitine profiles.

Rhabdomyolysis induced by rosuvastatin combined with entecavir: a case report.

BACKGROUND: Rhabdomyolysis is a serious and potentially life threatening condition that can be caused by drugs. We report a case of acute hepatitis B with rhabdomyolysis after treatment with rosuvastatin and entecavir. CASE PRESENTATION: A 72-year-old female was admitted to our hospital due to acute hepatitis B infection. She had taken atorvastatin for 3 months before being admitted to our hospital. After being administered entecavir (ETV) and rosuvastatin to replace atorvastatin, she suffered from muscle pain in both lower limbs and was diagnosed with rhabdomyolysis. After discontinuation of the two drugs, the patient's symptoms subsided and creatine kinase levels returned to normal. We hypothesize that the rhabdomyolysis was caused by the combination of rosuvastatin and ETV. CONCLUSIONS: We suggest that patients who use rosuvastatin and ETV be made aware of the complication of rhabdomyolysis.

Serum myoglobin as predictor of acute kidney injury and 90-day mortality in patients with rhabdomyolysis after exertional heatstroke: an over 10-year intensive care survey.

OBJECTIVE: Rhabdomyolysis (RM) in exertional heatstroke (EHS) often leads to multiple organ dysfunction including acute kidney injury (AKI). Studies have shown that serum creatine kinase (CK) >1000 U/L as a serological diagnostic criterion for RM does not reflect the risk of AKI or mortality. METHODS: This longitudinal cohort study included all patients with EHS who were admitted to intensive care unit between January 2008 and June 2019. Serum myoglobin (sMb) was studied as the serological marker of RM and compared with CK. Outcome events were AKI and 90-day mortality. RESULTS: A total of 161 patients were enrolled, of whom 52 (32.3%) had sMb ≥1000 ng/mL. Patients with sMb ≥1000 ng/mL had higher SOFA score, higher APACHE II score, lower GCS score, and higher incidence of disseminated intravascular coagulation, acute myocardial injury, acute liver injury, AKI, and 90-day mortality than patients with sMb <1000 ng/mL. Lymphocytes, neutrophils, D-Dimer were risk factors for AKI in patients with sMb ≥1000 ng/mL. Curve fitting showed a curved relationship between sMb and EHS-induced AKI but not CK. sMb ≥1000 ng/mL showed better predictive ability for AKI (area under curve: 0.786). APACHE II, SOFA, and GCS scores were risk factors for 90-day mortality in patients with sMb ≥1000 ng/mL. CONCLUSION: Serum myoglobin is a better predictor of AKI and 90-day mortality than CK in patients with RM after EHS.

Chlorpheniramine poisoning as a potential cause of rhabdomyolysis.

Chlorpheniramine is an H1 receptor antagonist of the alkylamine class. It is a widely used anti-allergy drug due to its strong antihistamine effect and mild adverse effects. In the case of chlorpheniramine overdose or poisoning, the primary manifestation is central nervous system symptoms. To date, no case of rhabdomyolysis induced by acute poisoning with chlorpheniramine has ever been reported. This study reports a case of acute chlorpheniramine poisoning at an oral dose of 4000 mg, which is the highest reported poisoning dose to date. The diagnosis of rhabdomyolysis (creatine kinase, 195,489 U/L) and acute kidney injury (serum creatinine, 150.1 umol/L) was confirmed based on laboratory results. After haemoperfusion and continuous renal replacement therapy, the patient's renal function fully recovered. This paper aims to analyse the clinical data of this patient and summarize its clinical characteristics. At the same time, the mechanism of chlorpheniramine-induced rhabdomyolysis is also explored in the context of the literature review.