Experience with carnitine palmitoyltransferase II deficiency: diagnostic challenges in the myopathic form.

OBJECTIVES: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form of CPT II deficiency at Ege University Hospital. METHODS: A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. RESULTS: Ten patients were examined for rhabdomyolysis of unknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C>T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C>T (p.Ser113Leu). CONCLUSIONS: Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.

Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report.

RATIONALE: Rhabdomyolysis can be an uncommon complication of coronavirus disease 2019 (COVID-19) infection. However, the diagnosis of rhabdomyolysis could be easily missed due to its atypical clinical presentations. We present a patient with a history of end-stage renal disease (ESRD) who contracted COVID-19 and subsequently developed rhabdomyolysis. We discuss and share our experience in the management of this patient. PATIENT CONCERNS: An 85-year-old male with ESRD undergoing routine hemodialysis was tested positive for COVID-19. The patient had clinical symptoms of fatigue, muscle pain, and difficulty walking. DIAGNOSIS: The serum creatine kinase (CK) level was markedly elevated to 32,492.9U/L, supporting the diagnosis of rhabdomyolysis. A computed tomography scan revealed muscle injuries throughout the body, confirming the diagnosis. INTERVENTIONS: The patient was managed through electrolyte corrections and continuous renal replacement therapy. OUTCOMES: Repeat tests showed decreased levels of serum CK and negative severe acute respiratory syndrome coronavirus 2. His clinical symptoms, including fatigue and muscle pain, had significantly improved. LESSONS: COVID-19 infection can cause muscle pain and fatigue, which can mask the symptoms of rhabdomyolysis. A missed diagnosis of rhabdomyolysis can be severe, especially in patients with ESRD. The serum CK level should be tested with clinical suspicion. Appropriate management, including adequate hydration and electrolyte balance, should be provided. Continuous renal replacement therapy should be considered in affected patients with renal insufficiency.

Acute myositis secondary to Epstein-Barr virus in the absence of infectious mononucleosis with severe rhabdomyolysis.

SummaryRhabdomyolysis is characterised by muscle breakdown which causes myoglobin light chain release and can result in renal injury. While some of the most common causes of rhabdomyolysis are trauma related, others include toxins, autoimmune processes or viral aetiologies. We present the case of a 20s-year-old man, with no significant medical history, who presented to the emergency department with a 1-week history of weakness, myalgias, nausea, vomiting and subjective fevers. A review of systems and physical exam were otherwise unremarkable, including being negative for sore throat, dysphagia and lymphadenopathy. On presentation, the patient was noted to have dark urine with a creatine kinase value of 452 458 U/L and an elevated creatinine at 7.23 mg/dL. The patient denied any trauma or increased physical activity. His toxin screen and autoimmune workup were negative. The patient's serological workup was significant for acute Epstein-Barr virus (EBV) infection, without additional viral coinfection or mononucleosis. During his hospitalisation course, the patient was managed with supportive care including haemodialysis. The patient made a full renal recovery and was discharged with scheduled outpatient follow-up. This case highlights the recognition of an acute EBV infection causing rhabdomyolysis in the absence of mononucleosis or concomitant infection.

Case Report: An Imported Case of Typhoid Fever Combined with Rhabdomyolysis and Multiple Organ Lesions in China.

Here, we report a case of blood culture-confirmed typhoid fever, rhabdomyolysis, and multiple organ damage that arrived in our country from overseas. A 23-year-old male patient presented at our hospital with fever and muscle pain; the condition progressed rapidly. Six days after the onset of symptoms, the patient developed rhabdomyolysis and liver/kidney damage; levels of creatine kinase (CK; maximum peak: 729,869 U/L) and myoglobin (> 3,000 ng/mL) were extremely high, although the extent of renal damage was relatively mild. Blood culture showed Salmonella typhi. The patient received a combination of meropenem and levofloxacin anti-infective therapy, as well as fluid and nutritional metabolic support. He gradually recovered and was discharged after two negative blood cultures. This case highlights the fact that typhoid-induced rhabdomyolysis is a serious, life-threatening disease and that the levels of CK and myoglobin are useful indicators for evaluating typhoid-induced rhabdomyolysis. Clinicians should remain vigilant regarding travel-related illnesses associated with enteric fever.

Rhabdomyolysis in McArdle disease caused by scuba diving.

McArdle disease is a glycogen storage disease that results in rhabdomyolysis during intense exercise. A number of different triggers have been described. We evaluated a patient with McArdle disease who presented with rhabdomyolysis after recreational scuba diving. There was no concern for barotrauma or decompression sickness. His symptoms resolved with standard-of-care management for non-diving-related rhabdomyolysis. Features of his experience provoked questions about the diving-related factors contributing to his presentation. We present the case and explore possible mechanisms of diving-related injury in patients with McArdle disease, including the possible effects of hyperoxia, hyperbaria, hypothermia and strenuous activity.

Rhabdomyolysis in a young woman after whole-body electromyostimulation training.

This is a case report of a hospitalised 31-year-old female with rhabdomyolysis following a single 20-minute training session wearing a whole-body electromyostimulation (WB-EMS) suit. The patient presented with severe muscle pain, dark-coloured urine, and among others elevated levels of plasma creatine kinase and myoglobin. This case report demonstrate that unaccustomed WB-EMS training may be harmful. Therefore, healthcare professionals as well as those using and operating the WB-EMS applications should be aware of the potential adverse events to the equipment, e.g. severe rhabdomyolysis.

[A case of very long chain acyl-CoA dehydrogenase deficiency diagnosed due to a trigger of hyperemesis gravidarum during pregnancy].

A 25-year-old Japanese woman with a history of repeated episodes of rhabdomyolysis since the age of 12 presented with rhabdomyolysis caused by hyperemesis gravidarum. Blood tests showed an elevated serum CK level (11,755 |IU/l; normal: 30-180 |IU/l). Carnitine fractionation analysis revealed low levels of total carnitine (18.3 |µmol/l; normal: 45-91 |µmol/l), free carnitine (13.1 |µmol/l; normal: 36-74 |µmol/l), and acylcarnitine (5.2 |µmol/l; normal: 6-23 |µmol/l). Tandem mass spectrometry showed high levels of C14:1 acylcarnitine (0.84 |nmol/ml: normal: <0.4 |nmol/ml) and a high C14:1/C2 ratio of 0.253 (normal: <0.013), indicating a potential diagnosis of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. In Japan, neonatal mass screening is performed to detect congenital metabolic diseases. With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. However, it is important to note that mass screening cannot detect all cases of this disease. For patients with recurrent rhabdomyolysis, it is essential to consider congenital diseases, including fatty acid metabolism disorders, as a potential diagnosis.

Acute HIV presenting as rhabdomyolysis.

A man, in his early 30s, with no significant medical history presented with a 2-week history of fatigue, chest and abdominal pain, associated with anorexia and vomiting. Initial laboratory testing was suggestive of rhabdomyolysis with acute renal failure and transaminitis. The aetiology of his rhabdomyolysis initially remained unexplained as there were no clear risk factors or inciting events. An extensive workup revealed acute HIV as the precipitant of rhabdomyolysis.

Clinical and Epidemiological Characteristics of Rhabdomyolysis: A Retrospective Study.

Background: Rhabdomyolysis (RM) refers to a clinical syndrome in which muscle cells are damaged by various causes and the clinical manifestations are mainly muscle pain, weakness, and dark urine. Acute kidney injury (AKI) is a serious complication of RM with complex mechanisms and high mortality. Therefore, understanding the pathogenesis and clinical manifestations, early diagnosis and treatment of RM are crucial to improve its prognosis. Method: Analysis of medical records of RM patients admitted to Tianjin Medical University General Hospital from October 2019 to October 2022. Statistical software SPSS 25.0 was used to analyze the data. The risk factors of RM-complicated AKI were analyzed by logistic regression. The receiver operating characteristic (ROC) curve was plotted, the area under the curve (AUC) was calculated, and the optimal cutoff value was determined by the Youden index. P < 0.05 indicates a statistically significant difference between the groups. Result: Among the 71 patients, the median age of the patients was 53.0 (30.0, 71.0) years and was 2.5 times higher in men than in women. Infection was the most common etiology. History of alcohol consumption, CK, and creatinine were independent influencing factors for AKI due to RM. Logistic regression analysis showed that CK combined with creatinine had a better predictive value than the single index. Conclusion: Our study revealed the clinical and laboratory characteristics of RM in the population attending the Tianjin Medical University General Hospital in the last three years, which is a reference for future multicenter, prospective studies.

[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.

COVID-19-associated rhabdomyolysis: A scoping review.

OBJECTIVES: SARS-CoV-2 infection ("COVID-19") and the hypoxemia that has attended some cases may predispose to rhabdomyolysis. We sought to identify reported cases of COVID-19-associated rhabdomyolysis, examining concurrent risk factors (RFs) and mortality outcomes. METHODS: We searched PubMed for articles conveying individual-level information on COVID-19-associated rhabdomyolysis, published between January 2020 and July 2022, with an English-language abstract. Two independent parties performed the search, and then abstracted information on cases including rhabdomyolysis RFs and mortality. RESULTS: In total, 117 individual reported cases of COVID-19-associated rhabdomyolysis were identified from 89 articles. A total of 80 cases (68.4%) had at least one reported non-COVID-19 RF (i.e. not considering COVID-19 or hypoxemia). On average, 1.27 additional RFs were reported, including age ≥65, metabolic syndrome features, hypothyroidism, previous rhabdomyolysis, hemoglobinopathy, trauma/compression, pregnancy, exertion, inborn errors of metabolism, concurrent (co-)infection, capillary leak syndrome, and selected rhabdomyolysis-associated medications. Concurrent RFs are understated, as many articles omitted comorbidities/medications. Of 109 cases with ascertainable survival status, 31 (28%) died. CONCLUSIONS: COVID-19 and hypoxemia confer risk of rhabdomyolysis, but additional rhabdomyolysis RFs are commonly present. Mortality is substantial irrespective of the presence of such RFs. Clinicians should be aware of COVID-19-associated rhabdomyolysis, and caution may be warranted in administering agents that may amplify rhabdomyolysis risk.

TANGO2 Deficiency Disorder: Two Cases of Developmental Delay Preceding Metabolic Crisis.

BACKGROUND: TANGO2 deficiency disorder is a rare genetic disease caused by biallelic defects in TANGO2 gene. METHODS: We report the clinical phenotype of two children with TANGO2 deficiency disorder. RESULTS: Patient 1 is a female child presenting with developmental delay and microcephaly during the second year of life, who evolved with severe cognitive impairment, facial dysmorphisms, spastic paraparesis, and atonic seizures. At age 13 years, she was hospitalized due to an episode of rhabdomyolysis complicated with cardiac arrhythmia and hypothyroidism. Patient 2 is a female child with dysmorphic facial features, cleft palate, and developmental delay who was diagnosed with DiGeorge syndrome. At age three years, she presented with an acute episode of severe rhabdomyolysis in the context of human herpesvirus 6 infection. After the resolution of this acute episode, she maintained recurrent muscle weakness with axial hypotonia and progressive spasticity of the lower extremities. In both patients, diagnosis of TANGO2 deficiency disorder was only confirmed after an acute metabolic crisis. CONCLUSIONS: A high index of suspicion for TANGO2 deficiency disorder is needed in patients with developmental delay or other neurological symptoms and episodic rhabdomyolysis.

COVID-19-Triggered Acute Liver Failure and Rhabdomyolysis: A Case Report and Review of the Literature.

COVID-19 is primarily known for its respiratory tract involvement, often leading to severe pneumonia and exacerbation of underlying diseases. However, emerging evidence suggests that COVID-19 can result in multiorgan failure, affecting organs beyond the respiratory system. We present the case of a 62-year-old male with COVID-19 who developed acute liver failure (ALF) and rhabdomyolysis in the absence of respiratory failure. Initially, the patient presented with significantly elevated aspartate transaminase (5398 U/L) and alanine transaminase (2197 U/L) levels. Furthermore, a prolonged prothrombin time international normalized ratio (INR) of 2.33 indicated the diagnosis of ALF without hepatic coma, according to Japanese diagnostic criteria. The patient also exhibited elevated creatine kinase (9498 U/L) and a mild increase in creatinine (1.25 mg/dL) levels, but both values improved with intravenous fluid support and molnupiravir administration. To our knowledge, this is the first reported case presenting with both ALF and rhabdomyolysis associated with COVID-19. In addition, we review the existing literature to summarize previously reported cases of ALF triggered by SARS-CoV-2. This case report underscores the significance of recognizing COVID-19 as a significant contributing factor in the development of multiorgan failure. Furthermore, it suggests that COVID-19 can lead to severe illness, irrespective of the absence of respiratory failure.

Desmond Beall - a Canadian's contribution to understanding rhabdomyolysis.

A pioneer in multiple areas of biochemical research, Desmond Beall made important contributions to Canadian medical history. His legacy laid the foundation for several modern scientific advances, extending from his doctoral work in Toronto on equine estrogen (which led to the development of conjugated estrogens) to landmark work on rhabdomyolysis during World War II. Though some theoretical understanding of the pathophysiology of traumatic rhabdomyolysis existed previously, Beall and his colleague Eric Bywaters substantially advanced this field of study with their publications on patients treated during the 1940 Blitz bombings. After the war, Beall shifted to working in industry and was able to translate his scientific advances into products affecting the lives of patients worldwide. Drawing from published works and personal communications with family members, this article is a memorial to a remarkable yet relatively unknown scientist.

Exertional Rhabdomyolysis Among Active Component Members of the U.S. Armed Forces, 2018-2022.

Exertional rhabdomyolysis is a pathologic muscle breakdown associated with strenuous physical activity. A largely preventable condition, it persists as an occupational hazard of military training and operations, especially in high heat environments among individuals exerting themselves to endurance limits. During the 5-year surveillance period, unadjusted incidence rates of exertional rhabdomyolysis among U.S. service members declined by approximately 15%, from 43.1 cases per 100,000 person-years (p-yrs) in 2018 to 36.5 cases per 100,000 p-yrs in 2022. Consistent with prior reports, subgroup- specific rates in 2022 were highest among men, those younger than 20 years, non-Hispanic Black service members, Marine Corps or Army members, and those in combat-specific and "other" occupations. Recruit trainees had the highest rates of exertional rhabdomyolysis in 2021 and 2022, with incidence rates 10 times higher than all other service members. Prompt recognition of the symptoms of exertional rhabdomyolysis (muscular pain or swelling, limited range of motion, or the excretion of darkened urine after strenuous physical activity, especially in hot, humid weather) by health care providers is crucial to avoid the most severe consequences of this potentially life-threatening condition.