Citations

Abstract Background and purpose Elevation of serum creatine kinase (CK) or hyperCKemia is considered a biological marker of myopathies. However, selective elevation of serum aldolase with normal CK has been reported in a few myopathies, including dermatomyositis, immune‐mediated myopathy with perimysial pathology and fasciitis with associated myopathy. The aim was to investigate the disease spectrum of myopathies with isolated aldolase elevation. Methods Medical records were reviewed to identify patients >18 years old seen between December 1994 and June 2020 who had pathologically proven myopathies with elevated aldolase and normal CK level. Patients with alternative causes of aldolase elevation were excluded. Results Thirty‐four patients with various types of myopathies were identified. Myopathies were treatable in 27 patients. The three most common etiologies were dermatomyositis ( n = 8), overlap myositis ( n = 4) and nonspecific myopathy ( n = 4). Perimysial pathology comprising inflammation, fragmentation, vasculitis, calcified perimysial vessels or extracellular amyloid deposition was found in 17/34 patients (50%). Eight dermatomyositis patients with selective elevated aldolase were compared to 24 sex‐ and age‐matched patients with dermatomyositis and hyperCKemia. Dermatomyositis patients with normal CK significantly ( p < 0.05) had less frequent cutaneous involvement (50.0% vs. 100.0%) and fibrillation potentials (50.0% vs. 90.5%) but higher median erythrocyte sedimentation rate (33.5 vs. 13.5 mm/h) and more common perifascicular mitochondrial pathology (37.5% vs. 4.2%). Conclusion Isolated aldolase elevation can be found in a greater variety of myopathies than initially thought and most were treatable. Dermatomyositis is the most common myopathy with selective elevation of aldolase in our cohort, which features some unique characteristics compared to dermatomyositis with hyperCKemia.

Abstract Background Myopathies associated with monoclonal gammopathy are relatively uncommon and underrecognized, treatable myopathies, and include sporadic late onset nemaline myopathy, light chain amyloid myopathy, and a recently described vacuolar myopathy with monoclonal gammopathy and stiffness (VAMGS). Herein, we report a new subtype of monoclonal gammopathy‐associated myopathy (MGAM) in a polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) patient. Method Case report. Results A 51‐year‐old woman presented with a 6‐month history of progressive bilateral foot drop, lower limb edema, and a 15‐lb weight loss. She denied muscle stiffness. Neurologic exam showed severe distal weakness, mild proximal weakness, and length‐dependent sensory deficits. Laboratory studies revealed biclonal gammopathy (IgG kappa and IgA lambda), thrombocytosis, and elevated vascular endothelial growth factor. Creatine kinase was normal. Electrodiagnostic studies identified mixed demyelinating and axonal polyradiculoneuropathy and a superimposed proximal myopathy. Gluteus medius biopsy demonstrated scattered fibers with glycogen‐filled vacuoles, similar to VAMGS, with additional rare myofibers containing polyglucosan bodies. She was diagnosed with POEMS syndrome and concomitant glycogen storage myopathy. Next‐generation sequencing of glycogen storage and polyglucosan body myopathy‐related genes was unrevealing. Proximal weakness resolved after autologous stem cell transplant. Conclusions This patient expands a spectrum of MGAM. Recognition of this condition and other subtypes of MGAM is of utmost important because they are treatable.

Abstract Objectives Mutations in VCP, HNRNPA2B1, HNRNPA1 , and SQSTM1 , encoding RNA‐binding proteins or proteins in quality‐control pathways, cause multisystem proteinopathies (MSP). They share pathological findings of protein aggregation and clinical combinations of inclusion body myopathy (IBM), neurodegeneration [motor neuron disorder (MND)/frontotemporal dementia (FTD)], and Paget disease of bone (PDB). Subsequently, additional genes were linked to similar but not full clinical‐pathological spectrum (MSP‐like disorders). We aimed to define the phenotypic‐genotypic spectrum of MSP and MSP‐like disorders at our institution, including long‐term follow‐up features. Methods We searched the Mayo Clinic database (January 2010–June 2022) to identify patients with mutations in MSP and MSP‐like disorders causative genes. Medical records were reviewed. Results Thirty‐one individuals (27 families) had pathogenic mutations in: VCP ( n = 17), SQSTM1 + TIA1 ( n = 5), TIA1 ( n = 5), MATR3, HNRNPA1, HSPB8 , and TFG ( n = 1, each). Myopathy occurred in all but 2 VCP ‐MSP patients with disease onset at age 52 (median). Weakness pattern was limb‐girdle in 12/15 VCP ‐MSP and HSPB8 patient, and distal‐predominant in other MSP and MSP‐like disorders. Twenty/24 muscle biopsies showed rimmed vacuolar myopathy. MND and FTD occurred in 5 (4 VCP , 1 TFG ) and 4 (3 VCP , 1 SQSTM1 + TIA1 ) patients, respectively. PDB manifested in 4 VCP ‐MSP. Diastolic dysfunction occurred in 2 VCP ‐MSP. After 11.5 years (median) from symptom onset, 15 patients ambulated without gait‐aids; loss of ambulation ( n = 5) and death ( n = 3) were recorded only in VCP ‐MSP. Interpretation VCP ‐MSP was the most common disorder; rimmed vacuolar myopathy was the most frequent manifestation; distal‐predominant weakness occurred frequently in non‐ VCP ‐MSP; and cardiac involvement was observed only in VCP ‐MSP.

Abstract Objectives Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus resistance protein A (MxA) expression among sarcoidosis patients. Methods We reviewed the Mayo Clinic database (May 1980–December 2020) to identify sarcoidosis patients with myopathic symptoms and pathological evidence of myopathy. Results Among 5885 sarcoidosis patients, 21 had symptomatic myopathy. Eight carried a diagnosis of sarcoidosis 5.5 years (median) prior to myopathy onset. Eleven patients had ScM. The remaining had non-sarcoid myopathies (five IBM, one immune-mediated necrotizing myopathy, one non-specific myositis, two non-specific myopathy and one steroid myopathy). Estimated frequency of IBM is 85 per 100 000 sarcoidosis patients. The following features were associated with non-sarcoid myopathies (P &lt; 0.05): (i) predominant finger flexor and quadriceps weakness, (ii) modified Rankin scale (mRS) &gt;2 at time of diagnosis, (iii) creatine kinase &gt;500 U/l, and (iv) absence of intramuscular granulomas. Sarcoplasmic MxA expression was observed in scattered myofibres in three patients, two of whom were tested for DM-specific autoantibodies and were negative. Immunosuppressive therapy led to improvement in mRS ≥1 in 5/10 ScM, none of the five IBM, and 3/3 remaining patients with non-sarcoid myopathies. Discussion Symptomatic myopathy occurred in 0.36% of sarcoidosis. IBM was the second most common cause of myopathies after ScM. Frequency of IBM in sarcoidosis is higher than in the general population. Recognition of features suggestive of alternative aetiologies can guide proper treatment. Our findings of abnormal MxA expression warrant a larger study.

See article on pages 111‐116 in this issue.