A High Creatine Kinase Concentration Might Be a Sign of McArdle Disease in Patient With Type 1 Diabetes

Increasing Creatine Kinase Concentrations at the 161-km Western States Endurance Run

Dear Editor, Patients with McArdle's disease are often diagnosed secondary to exercise intolerance, myalgia, fatigue, poor endurance, and muscle swelling, among other symptoms. In these patients, the resting serum creatine kinase (CK) levels are known to be elevated. There is little information regarding the effects of labor and delivery on the disease. We would like to report our experience in patients with McArdle's disease that were followed during their pregnancy and in the peripartum period. Following delivery, one of the patients developed sudden severe ankle pain which was consistent with and subsequently confirmed as acute compartment syndrome. The rise in serum creatine kinase by itself was not diagnostic of postpartum compartment complication but when combined with clinical findings, the condition was recognized and treated. McArdle's disease is a genetic condition that is predominantly passed in an autosomal recessive fashion [1,2]. Patients with McArdle's disease have inadequate amounts of skeletal muscle specific glycogen phosphorylase, myophosphorylase which subsequently leads to elevation in CK levels [1,3,4]. These patients suffer from exercise intolerance characterized during anaerobic activities and intense aerobic activities [1,3,4]. A high-resting serum CK level after demanding physical exertion is characteristic of McArdle's disease [1]. A diet consisting mostly of complex carbohydrates in …

McArdle disease (glycogen storage disease type V) is a pure myopathy caused by an inherited deficit of myophosphorylase. The disease exhibits clinical heterogeneity, but patients typically experience exercise intolerance, acute crises of early fatigue, and contractures, sometimes with rhabdomyolysis and myoglobinuria, triggered by static muscle contractions or dynamic exercise. We present the case of a 54-year-old man with a lifelong history of fatigability, worsening on exertion. Laboratory evaluation revealed significant elevations in levels of creatine kinase (7924 U/L), lactate dehydrogenase (624 U/L), and myoglobulin (671 ng/mL). A muscle biopsy confirmed the presence of McArdle disease. This case report illustrates how, due to embarrassment, the patient hid his symptoms for many years and was eventually extremely relieved and “liberated” once McArdle disease was diagnosed 40 years later.

Effects of ammonia and lactate on growth, metabolism, and productivity of BHK cells.

Dear Editor, Glycogen storage disease type V (GSD-V) is the most common disorder of muscle glycogenosis and is caused by alterations in the PYGM gene.1 Patients with GSD-V typically present with exercise intolerance, episodic rhabdomyolysis, and the second-wind phenomenon. Seizure has been well described as a provocative event for rhabdomyolysis, but it is not classical feature of GSD-V. Here we report recurrent episodes of rhabdomyolysis after seizures in a Korean patient with PYGM mutations. The male proband (II-2 in Fig. 1A) was the first child of nonconsanguineous healthy parents. He achieved normal motor milestones. At the age of 17 years he was hospitalized for rhabdomyolysis with a serum creatine kinase (CK) level of 718,000 IU/L after intense exercise and generalized tonic-clonic seizure (Supplementary Table 1 in the online-only Data Supplement). He did not have fixed muscle weakness. An electromyography study showed no spontaneous activities. Electroencephalography demonstrated a few spikes at the left frontocentral region. He was hydrated, and treated with anticonvulsants, but the serum CK level remained elevated (630 IU/L) at rest. The ischemic forearm exercise test demonstrated no increase in serum lactate level and a normal increase in serum ammonia level. At the age of 18 years he was readmitted to our clinic due to rhabdomyolysis and seizure. His serum CK level was 486,800 IU/L. Subtle muscle weakness was initially found in the shoulder girdle muscles, but recovered after 3 days. At the age of 28 years he was hospitalized for the third event of rhabdomyolysis (serum CK level: 124,500 IU/L) after a seizure. We performed targeted sequencing of 69 myopathy-related genes, including PYGM (Supplementary Table 2 and 3 in the online-only Data Supplement). DNA fragments in the target regions were enriched by solution-based hybridization capture, followed by sequencing with the Illumina Hiseq2000 platform. The sequencing data were analyzed using a standard pipeline (see in Supplementary Information in the online-only Data Suplement). Variants were then filtered further based on the patient's phenotype. We identified compound heterozygous PYGM mutations of c.1531delG and c.1999A>T (Fig. 1B). The c.1531delG mutation has been reported previously,2 but the c.1999A>T mutation is novel, since it was not detected in dbSNP138 or the 1000 Genomes Database (September 2014 release). In silico predictions support a deleterious effect of the c.1999A>T mutation on PYGM (Supplementary Table 4 in the online-only Data Supplement). Additionally, genomic evolutionary rate profiling indicated that the affected nucleotide is highly conserved (score=4.91) (Fig. 1C). Thus, we determined that the c.1531delG and c.1999A>T compound heterozygous PYGM mutations were the underlying cause of the observed myopathy. A deltoid muscle biopsy was performed at the age of 18 years. Light microscopy of the sample with hematoxylin and eosin staining revealed moderate variations of fiber size and shape as well as numerous scattered markedly necrotic myofibers with macrophage infiltration (Fig. 1D). The periodic acid-Schiff stain showed a slightly increased positive reaction in the remaining myofibers. Electron microscopy revealed the focal subsarcolemmal accumulation of glycogen (Fig. 1E) and necrotic myofibers exhibiting variable stages of degenerative changes (Fig. 1F). Fig. 1 Pedigree, sequencing chromatograms, conservation profile, and pathology. A: Pedigree of a Korean patient with compound heterozygous PYGM mutations. Arrows indicates the proband (square: male; circle: female; filled: affected; and nonfilled: unaffected). ... We have identified compound heterozygous PYGM mutations (c.1531delG and c.1999A>T) using targeted sequencing of 69 myopathy-related genes. GSD-V is caused by a deficiency of the muscle isoform of phosphorylase, which is encoded by PYGM. Human phosphorylase consists of three isoforms that are differentially expressed in the muscle, brain, and liver, with the muscle isoform being mainly expressed in muscle tissue. Therefore, GSD-V is usually considered to be a pure myopathy. However, both the brain and muscle isoforms were expressed in astrocytes, which predominantly contain glycogen in the adult brain.3 The occurrence of seizures has rarely been reported in patients with GSD-V,1,4 which suggests that the muscle isoform has an additional role in the brain; however, the precise nature of this role remains to be determined. In conclusion, this is the first report of novel compound heterozygous PYGM mutations in a Korean patient with recurrent seizure as rare provocative events of rhabdomyolysis.

Anaesthetic management of a known or suspected malignant hyperthermia susceptible patient

McArdle disease is an inborn disorder of muscle glycogen metabolism that produces exercise intolerance, and has been recently associated with low values ​​of lean mass (LM) and bone mineral content (BMC) and density (BMD) in affected adults. Here we aimed to study whether this bone health problem begins in childhood. Forty children and adolescents were evaluated: 10 McArdle disease and 30 control children (mean age of both groups, 13 ± 2y). Body composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase (CK) levels were determined in the patients as an estimate of muscle damage. Legs bone mass was significantly lower in patients than in controls (-36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM values in the legs than controls, whereas no difference was found for fat mass. CK levels were positively associated with LM in McArdle patients. A correlation was found between LM and BMD variables in the control group but not in McArdle patients. We have identified a 'non-osteogenic muscle hypertrophy' in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life.

This was a retrospective study to assess the diagnostic value of the non-ischaemic forearm exercise test in detecting McArdle's disease. The study is a retrospective diagnostic study over 15 years (1999-2013) on a referred sample of patients suffering from exercise intolerance and various muscle complaints, generally with elevated creatine kinase (CK). In all, 1226 patients underwent the non-ischaemic forearm exercise test. Blood lactate, ammonia and CK levels were analyzed. DNA analyses and/or muscle biopsies were assessed to confirm the diagnosis of McArdle's disease. The results of 60 volunteers were used to compare with the results of study subjects. In this cohort, 40 patients were finally diagnosed with McArdle's disease. Absolute values of lactate and ammonia rise were used to discriminate all McArdle patients from healthy patients. A sensitivity and specificity of respectively 100% and 99.7% were calculated. The 24-h CK level showed no significant difference from the CK level at the day of the test and confirms the safety of the test. This study has formally assessed the diagnostic value of the non-ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non-traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

Impact of transfusion of mediastinal shed blood on serum levels of cardiac enzymes

Background:We reported that creatine kinase (CK) levels were increased by JAK inhibitors in rheumatoid arthritis (RA) patients in a retrospective study 1. There are no reports of whether JAK selectivity...

BackgroundWell-leg compartment syndrome (WLCS) can occur due to compression and lower limb circulation disturbances caused by the surgical position during the procedure. Although rare, with an incidence of 1 in 3500 surgeries performed in the lithotomy position, it can lead to serious complications. Therefore, prevention and early diagnosis are critical. Symptoms of WLCS, such as leg pain, swelling, paresthesia, and serum creatine kinase (CK) levels are useful for diagnosis. This study aimed to investigate the risk factors for postoperative CK elevation in laparoscopic or robot-assisted colorectal cancer surgery performed in the lithotomy-Trendelenburg position.MethodsPostoperative CK levels were measured in 178 patients who underwent laparoscopic or robot-assisted colorectal cancer surgery between February 2022 and March 2023. We compared patient backgrounds, short-term outcomes, and thigh/calf circumferences between patients with CK levels ≥ 250 (n = 62) and those with CK levels < 250 (n = 116). We investigated risk factors for elevated CK levels using both univariate and multivariate analyses.ResultsFour patients with CK levels of 22405 U/L, 4685 U/L, 4050 U/L, and 3824 U/L reported symptoms, which improved with conservative treatment. The following independent prognostic factors were identified by multivariate analysis: male sex (odds ratio [OR], 4.403; 95% CI, 1.960 to 9.892), rectal surgery (OR, 2.779; 95% CI, 1.249 to 6.184), continuous head-down position duration ≥ 180 min (OR, 3.523; 95% CI, 1.552 to 7.997), and preoperative calf circumference ≥ 33 cm (OR, 2.482; 95% CI, 1.154 to 5.339).ConclusionsRisk factors for CK elevation after colorectal cancer surgery in the lithotomy position include male sex, rectal surgery, an extended continuous head-down position without position changes, and a larger preoperative calf circumference. This study highlights the potential importance of intraoperative position changes every 3 h for preventing elevated CK levels, although the preventive effect was not specifically examined.

PurposeExertional rhabdomyolysis can occur in individuals performing various types of exercise but it is unclear why some individuals develop this condition while others do not. Previous investigations have determined the role of several single nucleotide polymorphisms (SNPs) to explain inter-individual variability of serum creatine kinase (CK) concentrations after exertional muscle damage. However, there has been no research about the interrelationship among these SNPs. The purpose of this investigation was to analyze seven SNPs that are candidates for explaining individual variations of CK response after a marathon competition (ACE = 287bp Ins/Del, ACTN3 = p.R577X, CKMM = NcoI, IGF2 = C13790G, IL6 = 174G>C, MLCK = C37885A, TNFα = 308G>A).MethodsUsing Williams and Folland’s model, we determined the total genotype score from the accumulated combination of these seven SNPs for marathoners with a low CK response (n = 36; serum CK <400 U·L-1) vs. marathoners with a high CK response (n = 31; serum CK ≥400 U·L-1).ResultsAt the end of the race, low CK responders had lower serum CK (290±65 vs. 733±405 U·L-1; P<0.01) and myoglobin concentrations (443±328 vs. 1009±971 ng·mL-1, P<0.01) than high CK responders. Although the groups were similar in age, anthropometric characteristics, running experience and training habits, total genotype score was higher in low CK responders than in high CK responders (5.2±1.4 vs. 4.4±1.7 point, P = 0.02).ConclusionMarathoners with a lower CK response after the race had a more favorable polygenic profile than runners with high serum CK concentrations. This might suggest a significant role of genetic polymorphisms in the levels of exertional muscle damage and rhabdomyolysis. Yet other SNPs, in addition to exercise training, might also play a role in the values of CK after damaging exercise.

A case series in which a novel dosing strategy for managing mild, asymptomatic creatine kinase (CK) increases associated with daptomycin therapy is presented. Eight patients received a mean daptomycin dosage of 7.75 mg/kg/day for a median duration of 42 days. Seven of the eight patients were being treated for a bone and joint infection, and all but one had methicillin-resistant Staphylococcus aureus. All patients had asymptomatic increases in CK concentrations during daptomycin therapy (peak range, 400-1200 IU/L). A single daptomycin dose was withheld from each patient, and therapy was resumed 24 hours later, most often at the same dosage. The elevated CK values in these patients resolved, and all patients were able to complete daptomycin therapy without further increases in CK elevations. These findings indicate that withholding one dose of daptomycin during treatment may allow patients with asymptomatic, elevated CK concentrations to continue therapy with CK level normalization. Although the mechanism of daptomycin-mediated muscle injury is not fully understood, a reduction in daptomycin exposure via a one-dose cessation of therapy may allow for physiological restoration of sarcolemma membrane integrity that may be disrupted by daptomycin in individuals exhibiting CK elevation. A single daptomycin dose was withheld from eight patients with asymptomatic increases in serum CK concentrations, then daptomycin therapy was resumed 24 hours later, most often at the previous dosage. The CK concentrations returned to normal, and all patients were able to complete daptomycin therapy without further increases in CK concentrations.

Study DesignProspective, prognostic study, level II evidence.PurposeTo define the normal change in the creatine kinase (CK) levels in patients undergoing prone or supine lumbar or cervical spine surgery and to determine if positioning influences the postoperative changes in the CK levels.Overview of LiteratureSpine surgery is one of the most commonly performed and fastest growing areas of surgery in the United States. Thus, the various possible complications need to be understood, and risk factors for these complications need to be mitigated. One of the rare complications, reported in the literature as small case series and case reports, is rhabdomyolysis, diagnosed by high CK levels. Thus far, very few studies have examined the rise in CK levels following spine surgery, and to our knowledge, none has assessed the potential association of surgical positioning and the rise in CK levels.MethodsWe retrospectively analyzed 94 patients. We obtained their preoperative CK levels, and re-assessed their CK levels at postoperative day (POD) 1, 2, and 3, as well as at their 2-week follow-up. The data were analyzed with respect to the spine level and positioning to determine if positioning had any effect on the postoperative rise in the CK level.ResultsTotal 94 consecutive patients were enrolled in this study. The average preoperative CK level was 179.64, and the average CK level was 847.04 on POD 1. Prone positioning showed a greater rise in the CK levels following surgery than the supine positioning. In a similar manner, lumbar procedures led to a larger rise in the CK levels than cervical surgery. Prone/lumbar surgery showed the largest increase among all groups. Finally, revision surgery and instrumentation both increased the postoperative CK levels.ConclusionsThis study demonstrated that positioning can affect the postoperative CK level rise, with patients undergoing prone/lumbar surgery showing the greatest rise in the postoperative CK levels. This rise, however, may be related to paraspinal muscle damage, rather than the positioning itself.

Statin-Associated Myopathy in a Pediatric Preventive Cardiology Practice