Myopathy Syndrome Research Articles

Is It Statin Induced Polymyalgia Rheumatica or Just a Coincidence?

©2015 Turkish League Against Rheumatism. All rights reserved. A 53-year-old female presented with pain in her bilateral shoulders, hips and neck, stiffness (lasting one hour), and proximal weakness for three months. She declared that her symptoms had ensued one week after the usage of daily 40 mg atorvastatin for hyperlipidemia. As such, atorvastatin was discontinued; however, her complaints did not decline. Physical examination revealed painful and restricted shoulder and neck movements, weakness in shoulder and hip muscles, and a swollen, warm right knee. Laboratory investigations including creatine kinase (CK), rheumatoid factor and anti-nuclear antibody levels were within normal values, except for the increased C-reactive protein (0.744 mg/dL, N: 0-0.5) and erythrocyte sedimentation rate (75 mm/h, N: 0-20). X-rays of the hand, knee, hip and shoulder were non-contributory. Ultrasound illustrated biceps tenosynovitis and trochanteric bursitis bilaterally, and increased suprapatellar fluid in right knee (Figure 1). Overall, the patient was diagnosed with polymyalgia rheumatica (PMR) according to the 2012 European League Against Rheumatism/American College of Rheumatology classification criteria.1 Her symptoms and clinical findings (erythrocyte sedimentation rate and C-reactive protein levels) responded to medium dose of prednisolone (20 mg/d) treatment dramatically. Although statins have been reported to be associated with some musculoskeletal side effects such as myalgia, myositis, myopathy, and elevated CK, statin induced PMR is a very rare condition which has been reported only in a few anecdotal reports.2-4 Likewise, statin treatment might trigger the development of PMR in our patient. Since statin induced PMR and myalgia have similar clinical features, the exact diagnosis can be challenging. Statin induced myalgia presents with/without increased CK levels with normal erythrocyte sedimentation rate and C-reactive protein levels. Therefore, patients with statin induced myalgia may have normal serum CK levels, which sometimes make it difficult to distinguish PMR from myopathy syndromes. In case of drug discontinuation, symptoms heal in a period of one-week to four-month in statin, myopathy and treatment of steroid is rarely required.5 PMR patients do not recover spontaneously and corticosteroid treatment is usually needed.6

Monitoring of the treatment effect of the secondary myopathy syndrome in patients with juvenile rheumatoid arthritis

Dudnyk V. M., Bereznyckyi O. V., Vyzhga Yu. V. Monitoring of the treatment effect of the secondary myopathy syndrome in patients with juvenile rheumatoid arthritis. Journal of Education, Health and Sport. 2015;5(8):443-447. ISSN 2391-8306. DOI 10.5281/zenodo.31323 http://dx.doi.org/10.5281/zenodo.31323 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%288%29%3A443-447 https://pbn.nauka.gov.pl/works/632554 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011–2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 26.08.2015. Revised 05.09.2015. Accepted: 24.09.2015. Monitoring of the treatment effect of the secondary myopathy syndrome in patients with juvenile rheumatoid arthritis V. M. Dudnyk, O. V. Bereznyckyi, Yu. V. Vyzhga Vinnitsya national medical university N.I. Pirogov memorial Abstaract The syndrome of the secondary myopathy is one of the pathologies that is deeply spreaded in doctor’s practice and has a tendency to be increased being 30 – 60% of all chronicle pain syndromes in rheumatology practice. We provided examination of 43 patients with JRA to monitor effect of the treatment. The data presents that development of the secondary myopathy syndrome in patients with JRA is characterized with severe clinical currency of the disease, high inflammatory activity and significant influence on the quality of patient’s life so needed to be treated specific. Key words: secondary myopathy, juvenile rheumatoid arthritis.

Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome.

Histidyl-tRNA synthetase (HRS = Jo-1) represents a key autoantibody target in the anti-synthetase syndrome that is marked by myositis as well as extra-muscular organ complications including interstitial lung disease (ILD). Over the last 25 years, a wealth of clinical, epidemiological, genetic, and experimental data have collectively supported a role for Jo-1 in mediating deleterious cell-mediated, adaptive immune responses contributing to the disease phenotype of the anti-synthetase syndrome. Complementing these studies, more recent work suggests that unique, non-enzymatic functional properties of Jo-1 also endow this antigen with the capacity to activate components of the innate immune system, particularly cell surface as well as endosomal Toll-like receptors and their downstream signaling pathways. Combining these facets of Jo-1-mediated immunity now supports a more integrated model of disease pathogenesis that should lead to improved therapeutic targeting in the anti-synthetase syndrome and related subsets of idiopathic inflammatory myopathy.

Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders

BackgroundNeuromuscular disorders are a clinically, pathologically, and genetically heterogeneous group. Even for the experienced clinician, an accurate diagnosis is often challenging due to the complexity of these disorders. Here, we...

Cardiac abnormalities in patients with two different mitochondrial myopathy syndromes as detected by cardiovascular magnetic resonance imaging

Background Chronic progressive external ophtalmoplegia (CPEO) and Kearns-Sayre syndrome (KSS) belong to the broad heterogeneous group of mitochondrial myopathies (MM) a group of neuromuscular disorders resulting from primary dysfunction of the mitochondrial chain with impaired cellular energy metabolism. Recently, a potentially characteristic myocardial fibrosis pattern with intramural late gadolinium enhancement (LGE) in the left ventricular (LV) inferolateral wall was documented by cardiovascular magnetic resonance imaging (CMR) in these patients. The present study aimed at characterizing the presence and pattern of cardiac abnormalities in a larger CPEO/KSS patient population by means of CMR. Based on the fact that patients with other MM syndromes may show a concentric LV remodelling/hypertrophy (e.g. mitochondrial encephalopathy with lactic acidosis and stroke-like episodes MELAS) this aspect was also evaluated.

The evolution of capture myopathy in hooved mammals: a model for human stress cardiomyopathy?

Background and objectives: Capture myopathy (CM) syndromes in wildlife may be a model for human stress cardiomyopathy, including Takotsubo cardiomyopathy. Emotional stress or grief may trigger heart attack-like symptoms, and occasionally, sudden death in some humans. Similarly, wildlife exposed to predatory stresses, chase, or capture occasionally results in sudden death. To better understand the nature of vulnerability to stress-induced sudden death, we studied cases of CM in hooved mammals—ungulates—and hypothesized that CM would be associated with a syndrome of longevity-related traits.Methodology: We reconstructed the evolution of CM in ungulates then determined how a set of life history traits explained variation in the likelihood that CM was reported.Results: CM is broadly reported, but not in all genera, and phylogenetic analyses suggest that it is an evolutionarily labile trait. We found that the following traits were significantly associated with reports of CM: greater brain mass, faster maximum running speed, greater minimum group size and greater maximum longevity.Conclusions and implications: CM may be an unavoidable consequence of adaptations to reduce predation risk that include increased running speed, sociality and having larger brains. Moreover, longer-lived species seem to be more likely to be susceptible to CM. Exploring variable susceptibility to CM highlights the evolutionary origins of the disorder, potential basic mechanisms that underlie vulnerability to the phenomenon, and the potential for reduction of risk through modification of life history trajectory.

A Unique Myopathy Syndrome in a Patient Disclosing Clinical, Laboratory, and Genetic Findings of Late-Onset Pompe Disease, Together with a Lack of Dysferlin on Muscle Biopsy

A Unique Myopathy Syndrome in a Patient Disclosing Clinical, Laboratory, and Genetic Findings of Late-Onset Pompe Disease, Together with a Lack of Dysferlin on Muscle Biopsy

G.P.160: Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy

MEGF10 is a single transmembrane protein that is expressed in satellite cells of skeletal muscle, with 17 EGF-like domains in the extracellular region and 13 tyrosine residues in the cytoplasmic domain. Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans, including the syndrome of early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Previously we reported a family with a milder phenotype who harbored the compound heterozygous missense mutations C326R and C774R. A heterozygous C774R mutation was also found in a patient with EMARDD, paired with a heterozygous nonsense mutation in MEGF10, suggesting that C774R may be more damaging than C326R. Both mutations reside in the extracellular EGF-like domains of MEGF10. We found that these mutations were associated with decreased tyrosine phosphorylation of MEGF10 in vitro, and that C774R caused a greater impairment of tyrosine phosphorylation than C326R. We also found that Y1030 is the major tyrosine phosphorylation site in MEGF10 and is phosphorylated at least in part by c-Src. Co-expression of dominant-negative c-Src with MEGF10 shows decreased tyrosine phosphorylation of MEGF10, suggesting that MEGF10 is phosphorylated by endogenous c-Src. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not. In addition, overexpression of either wild type MEGF10 or Y1030D caused mild activation of ERK1/2. These findings indicate that MEGF10-mediated signaling via tyrosine phosphorylation plays an important role in myoblast proliferation, possibly via activation of ERK1/2. We conclude that MEGF10-mediated signaling via tyrosine phosphorylation helps to regulate myoblast proliferation. Our findings suggest that defects in this signaling pathway may contribute to the disease mechanism of MEGF10 myopathy.

G.P.155: A first Asian MEGF10 myopathy due to novel homozygous mutation

Recessive mutations in Multiple epidermal growth factor-like domains 10 (MEGF10) are known to cause the syndrome of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). We found a novel <i>MEGF10</i> mutation by whole exome sequencing (WES) in a Japanese patient with EMRDD. The patient is a 9-year-old boy from a non-consanguineous family. There is no family history of neuromuscular disease. He was born at 39 weeks of gestational age. Although peri- and neonatal periods were uneventful, he had frequent respiratory infections in early infancy. At age 1 year and 6 months he developed respiratory failure for which mechanical ventilation was necessary, in addition to facial and limbs muscle weakness, finger joint contracture, and areflexia. Muscle biopsy at age 1 year and 9 months showed unspecific changes with moderate fiber size variation and type 2 fiber atrophy. At age 2 years NIPPV was started. He could stand alone at 2 years and 5 months, walk alone at 2 years and 9 months old. At age 9 years he was found to have proximal muscle weakness with Gowers' sign, although he was still ambulant. Scoliosis was also developed. Serum CK levels were normal. Second muscle biopsy at age 9 years revealed marked fiber size variation, moth-eaten appearance in some fibers, adipose tissue infiltration, and endomysial fibrosis, reflecting chronic progressive course of myopathic disease. WES identified a homozygous frameshift mutation (c.129_130delTG p.Thr43 fsX9). On western blotting MEGF10 was absent in the patient's muscle, whereas it was increased in DMD muscle. Together with clinical and pathological manifestations compatible with EMARDD, we concluded that the disease is caused by <i>MEGF10</i> mutation in the patient. This is the first report of Asian EMARDD.

G.P.271: Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies

Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy (NM), cap myopathy, core-rod myopathy, congenital fibre-type disproportion, core-rod myopathy, distal arthrogryposes and Escobar syndrome. Here we correlate the clinical picture of these diseases with novel (16) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. A total of 27 Twenty-seven distinct pathogenic variants of TPM2, and 20 of TPM3, have been published or listed in the Leiden Open Variant Database ( http://www.dmd.nl/ ). Most are heterozygous changes associated with autosomal dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2 + sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotypes more often had contractures of the limb joints (18/19) and jaw (6/19) than those with non-hypercontractile ones (2/22 and 1/22), while patients with the non-hypercontractile molecular phenotypes more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding.

Exercise mitigates the adverse effects of hyperhomocysteinemia on macrophages, MMP-9, skeletal muscle, and white adipocytes.

Regular exercise is a great medicine with its benefits encompassing everything from prevention of cardiovascular risk to alleviation of different muscular myopathies. Interestingly, elevated levels of homocysteine (Hcy), also known as hyperhomocysteinemia (HHcy), antagonizes beta-2 adrenergic receptors (β2AR), gamma amino butyric acid (GABA), and peroxisome proliferator-activated receptor-gamma (PPARγ) receptors. HHcy also stimulates an elevation of the M1/M2 macrophage ratio, resulting in a more inflammatory profile. In this review we discuss several potential targets altered by HHcy that result in myopathy and excessive fat accumulation. Several of these HHcy mediated changes can be countered by exercise and culminate into mitigation of HHcy induced myopathy and metabolic syndrome. We suggest that exercise directly impacts levels of Hcy, matrix metalloproteinase 9 (MMP-9), macrophages, and G-protein coupled receptors (GPCRs, especially Gs). While HHcy promotes the M1 macrophage phenotype, it appears that exercise may diminish the M1/M2 ratio, resulting in a less inflammatory phenotype. HHcy through its influence on GPCRs, specifically β₂AR, PPARγ and GABA receptors, promotes accumulation of white fat, whereas exercise enhances the browning of white fat and counters HHcy-mediated effects on GPCRs. Alleviation of HHcy-associated pathologies with exercise also includes reversal of excessive MMP-9 activation. Moreover, exercise, by reducing plasma Hcy levels, may prevent skeletal muscle myopathy, improve exercise capacity and rescue the obese phenotype. The purpose of this review is to summarize the pathological conditions surrounding HHcy and to clarify the importance of regular exercise as a method of disease prevention.

Multimodal Imaging-Monitored Progression of Stroke-Like Episodes in a Case of MELAS Syndrome

We report imaging findings during, between, and after 2 stroke-like episodes in a 45-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome with an A32243G mitochondrial mutation 6 years before. In November 2010, for a first episode, she showed mixed aphasia with logorrhea, disinhibition, agitation, euphoria, and a large left temporoparietal lesion. Symptomatology progressively regressed under L-arginine treatment. She was readmitted in June 2011 for a second episode with great anxiety, disorientation, impaired face recognition, worsening mixed aphasia, and a new right temporal lesion. After additional L-carnitine treatment, she remained without relapse for 14 months.

A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations

Nuclear-encoded disorders of mitochondrial translation are clinically and genetically heterogeneous. Genetic causes include defects of mitochondrial aminoacyl-tRNA synthetases, and factors required for initiation, elongation and termination of protein synthesis as well as ribosome recycling. We report on a new case of myopathy, lactic acidosis and sideroblastic anemia (MLASA) syndrome caused by defective mitochondrial tyrosyl aminoacylation. The patient presented at 1 year with anemia initially attributed to iron deficiency. Bone marrow aspirate at 5 years revealed ringed sideroblasts but transfusion dependency did not occur until 11 years. Other clinical features included lactic acidosis, poor weight gain, hypertrophic cardiomyopathy and severe myopathy leading to respiratory failure necessitating ventilatory support. Long-range PCR excluded mitochondrial DNA rearrangements. Clinical diagnosis of MLASA prompted direct sequence analysis of the YARS2 gene encoding the mitochondrial tyrosyl-tRNA synthetase, which revealed homozygosity for a known pathogenic mutation, c.156C>G;p.F52L. Comparison with four previously reported cases demonstrated remarkable clinical homogeneity. First line investigation of MLASA should include direct sequence analysis of YARS2 and PUS1 (encoding a tRNA modification factor) rather than muscle biopsy. Early genetic diagnosis is essential for counseling and to facilitate appropriate supportive therapy. Reasons for segregation of specific clinical phenotypes with particular mitochondrial aminoacyl tRNA-synthetase defects remain unknown. © 2013 Wiley Periodicals, Inc.

Clavicle Lengthening by Distraction Osteogenesis for Congenital Clavicular Hypoplasia

Malformation and hypoplasia of the clavicle can result in pain, impaired function, restricted shoulder movement, subjective feeling of instability, and cosmetic deformity. There are no reports of clavicle lengthening by osteotomy and distraction osteogenesis (DO). This is a retrospective review of 5 patients (7 clavicles) who underwent clavicle lengthening by DO using a monolateral external fixator for clavicular hypoplasia. There were 3 males and 2 females with the mean age of 15 years (9 to 23 y) and mean follow-up of 35 months (12 to 66 mo). Preoperative diagnoses included Klippel-Feil syndrome, cleidocranial dysplasia with hemihypertrophy and torticollis, congenital myopathy and Noonans syndrome, and obstetric brachial plexus injury. Mean length gained was 31 mm (15 to 41 mm) that represents an average of 24.7% of overall bone length. Mean time in fixator was 174 days (161 to 263 d) and mean external fixation index was 56 d/cm. Two patients required internal fixation after fixator removal to consolidate union and 1 required additional internal fixation for atrophic regeneration. Mean preoperative oxford shoulder score improved from 28.5 to 41 and all patients were extremely satisfied with their result. Two patients developed pin-site infections. Clavicular lengthening by DO for congenital clavicular hypoplasia is a previously unreported technique that enables gradual correction of deformity without risking brachial plexus traction injury after acute correction. It has the potential to improve shoulder pain, function, range of movement, and cosmesis. Distraction ≥25% of overall bone length may require additional plate fixation to consolidate union. Level IV-therapeutic study.

MELAS syndrome diagnosed in ICU in a 56-year-old patient presenting with status epilepticus

The differential diagnosis of stroke in a middle-aged adult usually does not include the mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes syndrome (MELAS), because such a manifestation very rarely first occurs after the age of 40 [1, 2]. We report the case of a 56-year-old woman, brought to our hospital with irritability, aphasia, and ataxic gait. A brain computed tomography revealed a hypodense area on the left temporal lobe (Fig. 1). Ten hours later she developed convulsive status epilepticus and loss of consciousness. She was treated with phenytoin and transferred to the ICU, mechanically ventilated and sedated with propofol. Her past medical history was marked for a hearing deficit, for which a cochlear implant had been inserted 2 years earlier, and for an episode of loss of consciousness 6 months earlier. She was functional with daily activities. The patient was childless. Three out of her four sisters had died at early age. On ICU admission, physical examination revealed right hemiparesis. Pupils were equal and reactive and vital signs were within normal range. Fundoscopic examination was normal. Laboratory parameters were unremarkable, with the exception of white-cell count 18,900/mm (85 % neutrophils), aspartate aminotransferase 274 U/L, alanine aminotransferase 82 U/L, creatine kinase 9,705 U/L and lactate 3.3 mmol/L. Cerebrospinal fluid (CSF) examination was normal. The electroencephalogram showed frequent temporal spikes and slow wave complexes. Extensive imaging for brain vascular disease and laboratory investigation for autoimmune or infectious brain disease all proved negative. Magnetic resonance imaging was avoided due to the presence of the cochlear implant. On ICU day 7, the patient remained comatose. Persistent elevated blood lactate (2.5–5.3 mmol/L) was noted, despite clinical absence of seizures or haemodynamic instability. Repeat CSF revealed lactate 4.3 mmol/ L, not measured in the first sample. A mitochondrial encephalopathy was then suspected. A quadriceps muscle biopsy specimen revealed ‘‘ragged red fibres’’, corroborating the diagnosis of MELAS. Relatives declined further investigation with mitochondrial DNA analysis because the result would not affect the patient’s management, and there was no reason for genetic counseling. The patient had a slow neurological improvement; she weaned from mechanical ventilation and 44 days after ICU admission she was transferred to a rehabilitation center with a Glasgow Coma Scale of 13. First described in 1984, MELAS is a rare, maternally inherited clinical entity resulting from mutations in the mitochondrial DNA [1, 2]. The term ‘‘strokelike’’ refers to clinical and radiological impression of brain ischemia, albeit not conformed to a vascular territory. Although their pathogenesis remains unclear, relative deficiency of cellular adenosine triphoshate has been implicated [3]. According to diagnostic criteria, ‘‘strokelike’’ episodes have to appear before the age of 40 [2]. Few cases occur after the age of 50 [2–5] and none was first diagnosed in the ICU setting. Partial and complex partial status epilepticus are more commonly seen than generalized convulsive status epilepticus in MELAS [6]. ICU

Auditory Hallucinations Associated With Paget’s Disease

Auditory Hallucinations Associated With Paget’s Disease

Rare yet treatable: Hypothyroid myopathy (Hoffman′s syndrome)

Hypothyroid myopathy or Hoffman's syndrome is a rare manifestation of a common condition. It's diagnosis is also difficult. We present a case of Hoffman's disease with predominant proximal myopathy and myotonia.

Ictal and Interictal 99mTc-HMPAO Brain SPECT of a MELAS Case Presented With Epilepsy-like Visual Hallucination

A 55-year-old woman was diagnosed with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). She was referred for Tc-HMPAO brain SPECT because of visual hallucinations, which were suspected to be related to epileptic seizures. Ictal SPECT images showed remarkable hyperperfusion in the left occipital cortex, which returned to near-normal status on the interictal SPECT images after treatment with anticonvulsants. It is very rare to see such an ictal SPECT image of epileptic or epilepsy-like disorders, especially in the setting of MELAS syndrome with visual hallucination.

C.P.16 Mutations in the β-tropomyosin (TPM2) and γ-tropomyosin (TPM3) genes causing a spectrum of neuromuscular disorders

Published case reports of mutations in the tropomyosin genes describe a variety of neuromuscular disorders. The tropomyosins (Tms) exist as coiled-coil homo- or heterodimers forming head-to-tail polymers, running along the length of the actin molecule. They are encoded by four different genes; αTm (TPM1), βTm (TPM2), γTm (TPM3), and δTm (TPM4), generating more than 40 different tropomyosin isoforms. The tropomyosin genes TPM1, TPM2 and TPM3 are expressed in skeletal muscle encoding isoforms αTmfast, βTm, and δTmslow respectively. We extend the mutational and clinical spectrum of disorders caused by mutations of the β-tropomyosin (TPM2) and γ-tropomyosin (TPM3) genes and provide an overview of new and published cases. The clinical and histological findings of patients with cap myopathy, nemaline myopathy, CFTD, DA1A, DA2B and Escobar syndrome are correlated to the patients’ genotypes. We have also characterized the phosphorylation pattern of β-tropomyosin, both wt and β-tropomyosins containing patient mutations, and identified four novel phosphorylation sites.

Metabolomic profiling rationalized pyruvate efficacy in cybrid cells harboring MELAS mitochondrial DNA mutations

Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to elucidate metabolic effects of pyruvate treatment on cybrid human 143B osteosarcoma cells harboring normal (2SA) and MELAS mutant (2SD) mitochondria. The results demonstrated dramatic and sustainable effects of pyruvate administration on the energy metabolism of 2SD cells, corroborating pyruvate as a metabolically rational treatment regimen for improving symptoms associated with MELAS and possibly other mitochondrial diseases.