SEARCH · PubMed Health

Results for “Skeletal muscle dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed2006

Unraveling age-dependent variation of the mitochondrial proteome.

Blue-native and colorless-native gel electrophoresis combined with subsequent 2D-SDS-PAGE and MALDI mass spectrometry are successfully applied for understanding the role of mitochondria in cellular dysfunction, aging, and cellular death. The partial mitochondrial proteome maps of various tissues (liver, brain, kidney, heart, and skeletal muscle) obtained from rat serve now as a database for the elucidation of age-dependent changes, including alterations in protein-protein interactions as well as in posttranslational modifications.

Aged↗

PubMed1994

Importance of total leg muscle mass for exercise intolerance in chronic heart failure.

Patients with chronic heart failure symptoms tend to avoid voluntary effort and are thus subject to physical deconditioning. The presence of symptoms in daily life is thought to predispose to physical deconditioning and subsequent skeletal muscle loss. This study was designed to describe the relation among daily physical activities, skeletal muscle loss and exercise capacity in patients with chronic heart failure. We studied 14 patients with severe cardiac dysfunction (left ventricular ejection fraction < 40%) and 7 age-matched normal subjects. We measured total leg muscle mass by dual energy X-ray absorptiometry. The patients were divided into 7 asymptomatic and 7 symptomatic individuals using questionnaires for specific physical activities. Peak oxygen uptake and anaerobic threshold were significantly reduced in cardiac patients as compared with normal subjects. The reduction in exercise capacity was greater in the symptomatic patients than in asymptomatic patients. Leg muscle mass was significantly reduced (-17%) in the symptomatic patients, while it remained normal in the asymptomatic patients. Oxygen uptake in unit muscle mass at the level of anaerobic threshold and at peak exercise was decreased in both the asymptomatic (-21% and -21%, respectively) and symptomatic patients (-27% and -30%, respectively) but the difference between these two groups was not significant. In the asymptomatic patients, the reduced exercise capacity was accounted for primarily by muscle mass-independent factors such as an impaired nutritive blood flow to exercising muscles or metabolic abnormalities within the muscle cell. In the symptomatic patients, the marked reduction in exercise tolerance was attributable to a decrease in leg muscle mass and to hemodynamic or metabolic abnormalities. We conclude that the loss of leg muscle mass plays an important role in exercise intolerance in patients who are prone to physical deconditioning as a result of symptomatic heart failure.

Absorptiometry, Photon↗

PubMed2003

[Exercise training in heart failure].

BACKGROUND: In patients with chronic heart failure, exercise limitation cannot be exclusively attributed to cardiac dysfunction. During progression of the disease, peripheral factors have a growing impact on functional capacity. Chronic underperfusion of skeletal muscles, inactivity and a harmful effect of neuroendocrine stimulation lead to a myopathy syndrome characterized by atrophy, a shift in muscle fiber type and a loss of capillaries and mitochondria, which cause reduced muscle strength and aerobic capacity. Unlike left ventricular systolic function, which is a poor predictor of exercise tolerance in patients with chronic heart failure, parameters characterizing the myopathy syndrome correlate well with functional capacity. In the last 20 years, numerous studies have demonstrated that chronic heart failure patients in NYHA classes II and III benefit from physical training without deterioration of their cardiac function. EFFECTS OF EXERCISE TRAINING: Physical activity primarily improves muscle function and increases maximal as well as submaximal exercise capacity. Advantageous effects have also been observed with regard to neuroendocrine stimulation. The effect on central hemodynamics is much smaller and indirectly mediated by a trend towards decreased peripheral resistance. Left ventricular diameters, ejection fraction and filling pressures do not show significant changes. The gain in exercise capacity is usually accompanied by an improvement in symptom status and quality of life. Recent studies indicate that prognosis may also be improved by exercise training. CONVERSION INTO CLINICAL PRACTICE: Although continuous exercise training (mainly by use of cycle ergometry) has been investigated most thoroughly, there is an increasing number of studies reporting beneficial effects of interval and resistance training. Before starting a standardized training program, functional limitation and training intensity should be determined by an appropriate stress test. During the first training sessions, patients should always be supervised by a physician. In order to increase efficiency and feasibility of the exercise therapy, home-based training should be engaged as soon as a stable condition during repeated training sessions has been proven.

Chronic Disease↗

PubMed2004

[Role of physical training in cardiac rehabilitation in patients with congestive heart failure].

Patients with stable heart failure show decreased exercise tolerance and consequently quality of life. The reduced physical capacity in these patients is a result of decreased strength of skeletal muscles and even their atrophy. The physical activity is limited by metabolic disorders and histological changes in myocytes. Dysfunction of respiratory muscles plays a role in the development of exertional dyspnea. Patients with stable heart failure are recommended to perform low or moderate physical training, which improves exercise tolerance. Intensive physical training in patients with reduced left ventricular ejection fraction improves maximal oxygen consumption through increased left ventricular stroke and increased arteriovenous difference. Recent studies indicate that regular physical training has a positive physiological effect on exercise tolerance, and decreases dyspnea and fatigue, in many patients with heart failure.

Dyspnea↗

PubMed1995

Cardiac involvement in a large kindred with myotonic dystrophy. Quantitative assessment and relation to size of CTG repeat expansion.

OBJECTIVE: To evaluate and quantitate cardiac involvement in myotonic dystrophy and assess whether the size of the trinucleotide (cytosine-thymine-guanine [CTG]) repeat expansion is a significant predictor of cardiac abnormalities. DESIGN: Case-control study of a large kindred with myotonic dystrophy. PATIENTS: Ninety-one bloodline members of the kindred underwent clinical and cardiac evaluation with electrocardiograms, echocardiography (with Doppler in the majority of cases), and genetic and neurologic evaluations. Affected individuals were age-matched to normal family members. MAIN OUTCOME MEASURES: Electrocardiographic conduction abnormalities, wall motion abnormalities, mitral valve prolapse, and global parameters of systolic and diastolic function were determined by an observer blinded to all clinical data and genetic analysis. RESULTS: Compared with age-matched normals, patients with myotonic dystrophy (n = 25) were more likely to have conduction abnormality (52% vs 9%), mitral valve prolapse (32% vs 9%), and wall motion abnormality (28% vs 0%) (all P < .05). Left ventricular ejection fraction and stroke volume were reduced compared with normals matched for age and heart rate (P < .05), whereas Doppler indexes of diastolic function were only marginally altered. Using multivariate analysis, the number of CTG repeats (range, 69 to 1367; normal, < or = 37) was the strongest predictor of abnormalities in wall motion and electrocardiographic conduction (odds ratio of 16.5 and 5.07 per 500 repeats, respectively). The relation of mitral valve prolapse to the size of the CTG repeat was of borderline significance. Patients with more extensive neurologic findings (n = 12) had a higher incidence of wall motion and/or electrocardiographic conduction abnormalities (83% vs 43%; P = .04). CONCLUSIONS: Cardiac involvement in myotonic dystrophy affects predominantly the conduction system and myocardial function. Alterations in myocardial relaxation and diastolic properties, in contrast to skeletal muscle myotonia, are minor. In this kindred, the number of CTG repeats was a significant predictor of cardiac dysfunction in myotonic dystrophy.

Adolescent↗

PubMed1993

Are alterations of skeletal muscle ultrastructure in patients with heart failure reversible under treatment with ACE-inhibitors?

In patients with chronic heart failure, exercise capacity and clinical symptoms correlate poorly, if at all with the degree of left ventricular dysfunction. These observations might indicate that peripheral alterations (e.g. reduced perfusion of the exercising muscle) contribute to the functional state and exercise capacity of patients with chronic heart failure. Acute improvements in hemodynamics by means of therapy with vasodilators or positive inotropes, however, could not be translated into an enhanced oxygen consumption. These studies have prompted the hypothesis that in the setting of heart failure, intrinsic abnormalities of the exercising muscle develop that prevent acute improvement in peak VO2. Indeed, ultrastructural analysis of a large cohort of patients with chronic heart failure revealed that volume density of mitochondria and surface density of mitochondrial cristae (both are parameters for the oxidative capacity of skeletal muscle) were reduced by more than 20% as compared to healthy control subjects. In contrast to left ventricular contractility parameters, ultrastructural changes of the skeletal muscle correlated closely with peak oxygen consumption, indicating that abnormalities of the exercising muscle contribute to a decreased exercise capacity in this patient group. Chronic but not acute treatment with angiotensin converting enzyme (ACE) inhibitors increases blood flow to the exercising muscle and improves peak oxygen consumption. These protracted effects of ACE-inhibitors might be due to an inhibitory effect on the vascular renin angiotensin system leading to a beneficial remodelling of the vessel wall. Forearm vessels of patients with heart failure do not respond adequately to acetylcholine and reactive hyperemia, indicating an impaired endothelial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Leptin directly stimulates thermogenesis in skeletal muscle.

Using a method involving repeated oxygen uptake (MO(2)) determinations in skeletal muscle ex vivo, the addition of leptin was found to increase MO(2) in soleus muscles from lean mice. These effects were found to be inhibited by phosphatidylinositol 3-kinase inhibitors, absent in muscles from obese Lepr(db) mice which have the dysfunctional long form of leptin receptor, and blunted in muscles from diet-induced obese mice in the fed state but not during fasting. These findings indicate that leptin has direct thermogenic effects in skeletal muscle, and that these effects require both the long form of leptin receptors and phosphatidylinositol 3-kinase signalling.

Animals↗

PubMed2004

Human adult craniofacial muscle-derived cells: neural-cell adhesion-molecule (NCAM; CD56)-expressing cells appear to contain multipotential stem cells.

Skeletal muscle has been well characterized as a reservoir of myogenic precursors or satellite cells with the potential to participate in cellular repopulation therapies for muscle dysfunction. Recent evidence, however, suggests that the postnatal muscle compartment can be considered an alternative to bone marrow as a source of multipotent cells or muscle-derived stem cells (MDSCs). MDSCs, when primed with appropriate environmental cues, can differentiate into a variety of non-muscle cells. The present study describes the application of a new technique for the isolation of adult human myoblasts and putative MDSCs, based on microbead-immunomagnetic selection of CD56+ cells, derived from craniofacial skeletal muscle, and details changes in morphological/molecular phenotype of the purified cells when maintained in either a myogenic or a non-myogenic milieu. Multiple immunofluorescence microscopy and two-colour flow-cytometric analysis of proliferating CD56+ cultures revealed positive staining for myogenic markers (CD56, desmin and M-cadherin) as well as putative stem-cell markers [the antigens CD34, CD90 and CD106, and Flk-1 (fetal liver kinase-1)/VEGFR-2 (vascular-endothelial-growth-factor receptor)]. Confluent cultures subjected to cycles of adipogenic or osteogenic induction contained either adipocytes or osteoblasts and myotubes. In conclusion, the CD56+ subpopulation within adult human skeletal muscle is heterogeneous and is composed of both lineage-committed myogenic cells and multipotent cells (the candidate MDSCs), which are able to form non-muscle tissue such as fat and bone.

Adipocytes↗

PubMed2005

The capsaicin-sensitive afferent neuron in skeletal muscle is abnormal in heart failure.

BACKGROUND: In heart failure, the cardiovascular response to activation of the skeletal muscle exercise pressor reflex (EPR) is exaggerated. Group IV afferent neurons, primarily stimulated by the metabolic by-products of skeletal muscle work, contribute significantly to the EPR. Therefore, it was postulated that alterations in the activity of group IV neurons contribute to the EPR dysfunction manifest in heart failure. METHODS AND RESULTS: Group IV afferent fibers were ablated in neonatal Sprague-Dawley rats by subcutaneous administration of capsaicin. In neonatal capsaicin-treated adult animals, selective activation of the EPR, by electrically induced static muscle contraction, recapitulated the exaggerated increases in heart rate and blood pressure observed in rats with dilated cardiomyopathy (DCM). Furthermore, compared with control animals, both neonatal capsaicin-treated and DCM rats displayed a decreased pressor response to the intra-arterial administration of capsaicin within the hindlimb, a maneuver that selectively excites group IV afferent neurons. Moreover, expression of mRNA for the capsaicin receptor TRPv1, a marker of group IV fibers, was downregulated in DCM animals compared with controls. CONCLUSIONS: These findings suggest that EPR dysfunction in heart failure results in part from functional and molecular alterations in group IV fibers. Furthermore, the responsiveness of these metabolically sensitive neurons appears to be blunted in DCM, indicating that their contribution to the EPR may be reduced. This occurs despite an overall exaggeration of the EPR in heart failure. These insights into the basic mechanisms of EPR dysfunction are essential to the development of effective therapeutic strategies aimed at improving exercise capacity in heart failure.

Animals↗

PubMed1998

Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention.

Revascularization of a limb after a severe and prolonged period of ischemia may be associated with high rates of mortality and amputation, because of the development of a postrevascularization syndrome, regardless the cause of occlusion (ischemia, trauma, iatrogenic) or the methods used to achieve reperfusion (fibrinolysis, surgery, resuscitative therapy). This "revascularization" syndrome includes several complications, both local (explosive swelling of the limb, compartment syndrome and skeletal muscle infarction (rhabdomyolysis) and general (acidosis, hypercalcemia, hypovolaemic shock, renal, hepatointestinal and pulmonary failures, arrhythmias and cardiac arrest (multiple organ dysfunction). Current therapies are directed against complications after they occurred, once revascularization is completed: fasciotomy, mannitol and diuretics administration for forced diuresis, fluid administration to correct hypovolaemia, use of resins, insulin and glucose or haemodialysis to deal with hypercalcemia, administration of buffers (THAM, bicarbonate) to correct acidosis, control of hypercalcaemia with orthophosphates and calcitonin.... Nevertheless, a substantial percentage of the injury is generated upon reperfusion and the muscle may remain viable after prolonged period of ischemia. Intra and extraacellular swelling, tissue acidosis, free radical mediated damage, loss of adenine nucleotide precursors, and intracellular calcium overload have been suggested to be the mechanisms responsible for reperfusion injury. Careful control of both the composition and the physical conditions of the initial reperfusion (controlled reperfusion) may result, in selected cases, in improvements in the metabolism, structure and function of the limb after reperfusion.

Acute Kidney Injury↗

PubMed1988

Oculo-facio-skeletal myorhythmia as a cerebral complication of systemic Whipple's disease.

A fifth case of oculomasticatory myorhythmia associated with cerebral Whipple's disease is reported. This peculiar abnormal movement has never been described in association with cerebral dysfunction other than Whipple's disease. The present case exhibited rhythmic convergence of the eyes and synchronous (1-2 Hz) contractions of the masticatory muscles and of the proximal and distal skeletal muscles. These abnormal movements occurred 13 years after the beginning of the disease. They were persistent and unchanged until the death of the patient 3 months later. No treatment was effective to suppress the involuntary movements (clonazepam, baclofen, antibiotics). Associated neurological signs included global supranuclear ophthalmoplegia, facial weakness, bilateral ptosis, absent gag reflex, and intellectual deterioration.

Brain↗

PubMed2002

Clenbuterol attenuates muscle atrophy and dysfunction in hindlimb-suspended rats.

BACKGROUND: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity. HYPOTHESIS: This study tested the hypothesis that a beta-adrenergic agonist (clenbuterol) could attenuate the effects of 14 d of unweighting on mixed fiber type skeletal muscle. METHODS: Female, Sprague-Dawley rats were maintained in cages as: 1. controls (C; n = 12); 2. hindlimb suspended via tail casting (HLU; n = 12); 3. clenbuterol injected daily (3 mg x kg(-1)) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg x kg(-1)) (HLU + CL; n = 12). RESULTS: At the end of the study, both CL and HLU + CL had higher body weights compared with HLU (p < 0.05). Gastrocnemius mass (wet weight and muscle weight/body weight) and maximal tetanic force were significantly decreased during HLU (p < 0.05) (mean +/- SE; mass: C = 1.6 +/- 0.04 g, HLU = 1.2 +/- 0.05 g force: C = 3483 +/- 113 g, HLU = 2765 +/- 52 g). Clenbuterol attenuated the decrease in both mass and force generation (mass: HLU + CL = 1.4 +/- 0.04 g; force: HLU + CL = 3162 +/- 135). Twitch tension during HLU (1057 +/- 72 g) was significantly less (p < 0.05) than during C (1362 +/- 61 g), and clenbuterol did not attenuate this loss. HLU caused a decrease (p < 0.05) in force at 30 Hz and decreased one-half relaxation time (1/2 RT) (p < 0.05) from 30 +/- 2 to 25 +/- 2 ms. Clenbuterol caused further decreases (p < 0.05) in both force (20 and 30 Hz) and 1/2 RT. CONCLUSIONS: These data suggest that a beta-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle.

Adrenergic beta-Agonists↗

PubMed2004

Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction.

OBJECTIVE: Transforming growth factor (TGF)-beta promotes the deposition of extracellular matrix protein and also acts as an anti-inflammatory cytokine. These biological effects might be involved in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). However, its pathophysiological significance remains obscure in post-MI hearts. METHODS: Anterior MI was produced in mice by ligating the left coronary artery. TGF-beta mRNA levels increased in both infarcted and noninfarcted LV after MI. To block TGF-beta signaling during the early phase of MI, an extracellular domain of TGF-beta type II receptor (TbetaIIR) plasmid was transfected into the limb skeletal muscles 7 days before ligation. RESULTS: TbetaIIR increased the mortality during 24 h of MI, as well as exacerbated LV dilatation and contractile dysfunction, the infiltration of neutrophils, and gene expression of tumor necrosis factor-alpha, interleukin-1beta, and monocyte chemoattractant protein-1 compared with nontreated MI mice despite the comparable infarct size. Next, to block TGF-beta signaling during the later phase, TbetaIIR was transfected into mice at days 0 and 7 after ligation. At 4 weeks, LV dilatation and contractile dysfunction in association with myocyte hypertrophy and interstitial fibrosis of noninfarcted LV seen in MI mice were prevented by TbetaIIR. CONCLUSIONS: The activation of TGF-beta is protective against ischemic myocardial damage during the early phase. However, the beneficial effects might be lost, when its expression is sustained, thereby leading to LV remodeling and failure after MI.

Animals↗

PubMedDate not supplied

Protein metabolism in alcoholism: effects on specific tissues and the whole body.

Ethanol is one of the few nutrients that is profoundly toxic. Alcohol causes both whole-body and tissue-specific changes in protein metabolism. Chronic ethanol missuse increases nitrogen excretion with concomitant loss of lean tissue mass. Even acute doses of alcohol elicit increased nitrogen excretion. The loss of skeletal muscle protein (i.e., chronic alcoholic myopathy) is one of several adverse reactions to alcohol and occurs in up to two-thirds of all ethanol misusers. There are a variety of other diseases and tissue abnormalities that are entirely due to ethanol-induced changes in the amounts of individual proteins or groups of tissue proteins; for example, increased hepatic collagen in cirrhosis, reduction in myosin in cardiomyopathy, and loss of skeletal collagen in osteoporosis. Ethanol induces changes in protein metabolism in probably all organ or tissue systems. Clinical studies in alcoholic patients without overt liver disease show reduced rates of skeletal muscle protein synthesis though whole-body protein turnover does not appear to be significantly affected. Protein turnover studies in alcohol misusers are, however, subject to artifactual misinterpretations due to non-abstinence, dual substance misuse (e.g., cocaine or tobacco), specific nutritional deficiencies, or the presence of overt organ dysfunction. As a consequence, the most reliable data examining the effects of alcohol on protein metabolism is derived from animal studies, where nutritional elements of the dosing regimen can be strictly controlled. These studies indicate that, both chronically and acutely, alcohol causes reductions in skeletal muscle protein synthesis, as well as of skin, bone, and the small intestine. Chronically, animal studies also show increased urinary nitrogen excretion and loss of skeletal muscle protein. With respect to skeletal muscle, the reductions in protein synthesis do not appear to be due to the generation of reactive oxygen species, are not prevented with nitric oxide synthase inhibitors, and may be indirectly mediated by the reactive metabolite acetaldehyde. Changes in skeletal muscle protein metabolism have profound implications for whole body physiology, while protein turnover changes in organs such as the heart (exemplified by complex alterations in protein profiles) have important implications for cardiovascular function and morbidity.

Alcoholism↗

PubMed2003

Transcription factors c-Jun/activator protein-1 and nuclear factor-kappa B in oxidative stress response in mitochondrial diseases.

Mitochondrial dysfunction leads to oxygen free radical (ROS) generation with consequent oxidative stress and cellular damage. Recently, activation of the cellular antioxidant system and apoptosis were demonstrated in skeletal muscle fibres from patients with mitochondrial diseases, but the underlying mechanisms remain unknown. Hydrogen peroxide, a by-product of ROS generation, is a chemical inducer of gene expression able to activate apoptosis and to promote the antioxidant response through the activation of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) transcription factor. Using immunohistochemistry and confocal microscopy, we evaluated the expression of NF-kappaB and AP-1 in muscle biopsies from patients with mitochondrial disease. In addition, we examined the expression of factors involved in their activation, such as NF-kappaB inducing kinase (NIK) and phosphorylated Jun-N-terminal kinase (p-JNK). Most fibres with respiratory chain dysfunction displayed nuclear staining for activated c-Jun/AP-1, but not for NF-kappaB. The same fibres reacted for p-JNK. Only some ragged red fibres immunoreacted for NIK. These data suggest that AP-1 is involved in the oxidative stress response in muscle fibres from patients with mitochondrial disease.

Humans↗

PubMed1996

Gastrointestinal dysfunction in Parkinson's disease.

Gastrointestinal dysfunction is common and clinically important in patients with PD. Evidence continues to accumulate to indicate that these symptoms reflect, for the most part, the direct involvement of the gastrointestinal tract by the PD process. Gastrointestinal symptomatology may arise not only as a consequence of the effects of PD on skeletal muscles in the oropharynx, anorectum, and pelvic floor but also through the direct involvement of the autonomic and enteric nervous systems in the PD process. While many aspects of gastrointestinal dysfunction in PD continue to be delineated, therapeutic approaches to gut symptoms in this common disorder remain in their infancy. Gut involvement in PD can be seen to serve as a paradigm for gut-CNS interactions. The recent demonstration of neuropathologic abnormalities in the enteric nervous system analogous to those regarded as pathognomonic of the parkinsonian process in the CNS suggests that the enteric and central nervous systems may demonstrate parallel pathologic changes in a number of disease processes previously regarded as confined to the central and somatic nervous systems. In this way, the enteric nervous system may well serve as a more accessible "window" to a variety of degenerative neurologic disorders. With respect to PD itself, we can begin to relate both the neurologic and gastrointestinal manifestations of this disorder to defects at a number of levels (Table 1).

Constipation↗

PubMed2005

Marathoners or couch potatoes: what is the role of exercise in the management of heart failure?

Patients with chronic heart failure have diminished exercise capacity as a major aspect of their clinical syndrome, regardless of the cause of their left ventricular contractile dysfunction. The mechanisms for the reduction in exercise capacity are multifactorial and include central cardiac, peripheral vascular, respiratory, and skeletal muscle maladaptations that accompany the pathophysiology of heart failure. Increased sympathetic nervous system activity and elevations in circulating neurohormones and cytokines also influence the cardiovascular and metabolic responses to exercise in these patients. Despite the improvements in clinical outcomes with beta-blockers and resynchronization therapy in heart failure patients, their exercise capacity remains substantially reduced when compared with normal age-matched patients. Exercise training has the potential to reverse or improve most of the abnormal physiologic responses to exercise in these patients, and it may serve as adjunctive therapy to standard medical care of these patients. In addition, a body of evidence is being accumulated that suggests that exercise training itself has important secondary prevention benefit in these patients. This review identifies the potential mechanisms whereby exercise training may improve exercise capacity in patients with chronic heart failure and presents the current information regarding clinical outcomes of this therapy.

Adaptation, Physiological↗

PubMed1999

Kearns-Sayre syndrome with features of Pearson's marrow-pancreas syndrome and a novel 2905-base pair mitochondrial DNA deletion.

Kearns-Sayre syndrome (KSS) and Pearson's marrow-pancreas syndrome (PMPS) are rare disorders caused by the same molecular defect, one of several deletion mutations in mitochondrial DNA (mtDNA). KSS is an encephalomyopathy with ophthalmoplegia, retinal degeneration, ataxia, and endocrine abnormalities. PMPS is a disorder of childhood characterized by refractory anemia, vacuolization of bone marrow cells, and exocrine pancreas dysfunction. Children with PMPS that have a mild phenotype, or are supported through bone marrow failure, often develop the encephalomyopathic features of KSS. The subject of numerous reports in the neuromuscular, genetic, and pediatric literature in recent years, very few cases of either disorder have ever been studied at autopsy. We report the results of our studies of a patient with clinically documented KSS who presented with renal dysfunction and was found to have a novel mtDNA deletion and degenerative changes in the central nervous system, retina, skeletal muscle, and pancreas.

Adolescent↗