Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.
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PMID:Mitochondriopathies. 1500 63

Combinations of symptoms such as general malaise, fever, weight loss and cervical lymphadenopathy have extensive differential diagnoses. In three children, girls aged 11, 13 and 17 years who presented with these symptoms, three different diagnoses were obtained. The first had Hodgkin's disease, the second mixed connective tissue disease (MCTD), and the third Hodgkin's disease in combination with systemic lupus erythematosus (SLE). A systematic approach is necessary for the diagnosis of such conditions. Careful history taking can provide valuable information while a physical examination provides essential clues for the final diagnosis. In particular, nail-fold lesions, tendon nodules and signs of myopathy should be looked for in patients suspected of MCTD and/or SLE. In Hodgkin's disease, generalized or localised lymphadenopathy combined with a short history of extreme fatigue are the most important. Additional investigations should be individualized in order to minimise the diagnostic delay and make possible early treatment.
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PMID:[Three children with general malaise, fever, weight loss and cervical lymphadenopathy]. 1521 73

Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid alpha-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human alpha-glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair-bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of alpha-glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human alpha-glucosidase from rabbit milk has a therapeutic effect in late-onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals.
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PMID:Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up. 1504 88

Muscle diseases are an expanding field, mainly due to the progress in genetics and biochemistry. Evaluation starts with a thorough history of the patient's symptoms and signs. The leading clinical manifestations are weakness, atrophy, myalgia, fatigue, more rarely myotonia and in the child hypotonia or walking difficulty. A detailed family history might give clues to an underlying genetic etiology. Diagnostic workup begins with the measurement of serum creatine kinase. Electroneuromyography is an important investigation procedure which includes motor and sensory nerve conduction studies and concentric needle electromyography. Muscle biopsy is performed in all patients with clinical evidence of myopathy. A fine-needle technique is generally used, more often than a surgical biopsy. Molecular analysis of candidate genes is becoming a major diagnostic tool in many muscle disorders. Muscle imaging, in particular MR, provides diagnostic and follow-up information, especially in dystrophic, metabolic and inflammatory myopathies. Exercise testing can be useful in some metabolic myopathies. There is no standard protocol for the choice and course of investigations which must always be based on a detailed clinical evaluation. It is important to establish a precise diagnosis in order to inform the patient about the nature and the evolution of the disease, the therapeutic options and to propose, when indicated, genetic counseling.
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PMID:[How should a muscular disease be studied?]. 1509 27

Intensity of perceived inspiratory difficulty was investigated in 17 patients with severe respiratory insufficiency due to muscle disease, compared with healthy matched controls. Subjects breathed through a threshold valve generating a constant inspiratory negative pressure proportional to their maximal inspiratory pressure. Four load levels ranging from 10 to 40% of the maximal inspiratory pressure were applied in random order. Patients had significantly less perceived inspiratory difficulty than controls at each load level expressed as a percentage of maximal inspiratory pressure P < 0.001. However, when the load was expressed as the absolute value, the slope of the Borg scale score versus mouth pressure was similar in the two groups (P = 0.11). The ventilatory pattern remained unchanged in each group as the load increased. We conclude that in patients with myopathy, loads leading to respiratory muscle fatigue (40% of maximal inspiratory pressure) may fail to produce perceived inspiratory difficulty.
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PMID:Perceived inspiratory difficulty in neuromuscular patients with primary muscle disorders. 1509 86

Rippling muscle disease (RMD) is a rare muscle disorder characterised by muscle stiffness, exercise induced myalgia, and cramp-like sensations. It is genetically heterogeneous and can be acquired, but most cases show autosomal dominant inheritance due to mutations in the caveolin-3 (CAV3) gene. We report a novel heterozygous missense mutation in CAV3 in a Belgian family with autosomal dominant RMD. A 40 year old woman complained of fatigue, exercise induced muscle pain, and muscle cramps since the age of 35. Neurological examination revealed percussion induced rapid muscle contractions (PIRCs) and localised muscle mounding on percussion; muscle rippling was not observed. Creatine kinase (CK) was elevated but electromyography and nerve conduction studies were normal. Fluorescence immunohistochemistry revealed reduced caveolin-3 and dysferlin staining in a quadriceps muscle biopsy. Western blot analysis confirmed severely reduced caveolin-3 levels, whereas dysferlin was normal. Sequence analysis of the two coding exons of CAV3 revealed a hitherto unreported heterozygous C82A transversion in the first exon, predicting a Pro28Thr amino acid exchange. Thr patient's first degree relatives did not present with neuromuscular complaints, but PIRCs, muscle mounding, and muscle rippling were found in the mother, who also carried the CAV3 mutation.
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PMID:Novel missense mutation in the caveolin-3 gene in a Belgian family with rippling muscle disease. 1531 33

We present a laryngectomized patient with unspecific complaints of fatigue whose laboratory findings were out of proportion with the clinical presentation. The enormously high blood levels of creatine kinase (CPK) (8000 IU/l, normal range 30-190 IU/l) and thyroid-stimulating hormone (100 mU/l, normal range 0.5-4.5 mU/l) led to diagnosis and treatment of and recovery from hypothyroid myopathy. Hypothyroidism reduces the ability of the muscle to maintain its adequate energetic economy, via several suggested mechanisms. This may lead to injury (myopathy) that allows enzymes such as CPK to leak out of cells and causes elevation of their serum levels. To our knowledge, this is the first reported case of a patient previously treated for head and neck cancer who developed hypothyroid myopathy, presenting with exceptionally elevated CPK levels. This is noteworthy, since hypothyroidism may be easily avoided by a comprehensive follow-up of patients treated for head and neck cancer.
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PMID:Exceptionally elevated creatine kinase levels in a laryngectomized patient: hypothyroid myopathy. 1545 46

Bilateral diaphragmatic paralysis (BDP) can occur in the course of motor neuron disease, myopathy, or from mechanical damage or the use of "ice slush" during cardiac surgery. BDP has been observed during and after infections, associated with systemic lupus erythematosus and mediastinal tumors, or may have idiopathic etiology. It is a serious and life-threatening condition. A 62-yr-old man presented with slowly progressive dyspnoea that worsened in the supine position and on bending forward. Chest X-rays, fluoroscopy, lung-function parameters and blood-gas analysis revealed respiratory failure. BDP was confirmed from a phrenic nerve stimulation test and measurement of transdiaphragmatic pressure (Pdi). Since there was no evidence of an obvious etiology, BDP was considered idiopathic. Other muscles were not involved. The pathological basis was probably focal demyelination in segments of the phrenic nerve. Because of increasing diaphragmatic muscle fatigue, the patient was treated with a nasal mask providing bi-level positive airway pressure (BiPAP) ventilation during the night. Clinical suspicion of BDP should always be raised in patients suffering slowly progressive dyspnoea without any obvious cardiac, metabolic or traumatic predisposing factors, and orthopnoea and dyspnoea on bending forward. Electromyographic tests and measurement of Pdi can reveal the correct diagnosis.
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PMID:Spontaneous bilateral diaphragmatic paralysis: a rare cause of respiratory failure. 1547 Nov 85

We studied two adult patients with myalgia and muscular fatigability during prolonged physical exercise. Serum creatine kinase was increased and muscle biopsy revealed a lipid storage myopathy affecting predominantly the type I fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the normal mean values, while serum carnitine levels were either normal or decreased. Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in both patients, and a subsequent muscle biopsy confirmed a marked reduction of lipid storage, along with increased muscle carnitine levels. The analysis of renal carnitine excretion and the exclusion of possible secondary carnitine deficiencies in both patients are compatible with mild defects of the carnitine transporter in one patient and of carnitine biosynthesis in the other. Since myalgia and muscular fatigue are frequent but unspecified complaints of otherwise clinically unremarkable adult patients, it is important to identify myopathies associated with primary carnitine deficiency because they may be amenable to treatment.
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PMID:Primary carnitine deficiency: adult onset lipid storage myopathy with a mild clinical course. 1551 80

Late-onset Pompe's disease (acid maltase deficiency, glycogen storage disease type II) is a slowly progressive myopathy caused by deficiency of acid alpha-glucosidase. Current developments in enzyme replacement therapy require detailed knowledge of the kind and severity of symptoms and the natural course of the disease in the patient population. A detailed questionnaire covering the patients' medical history and current situation was developed and information was gathered from 54 Dutch patients. The mean age of the participants was 48.6 +/- 15.6 years. The first complaints started at a mean age of 28.1 +/- 14.3 years and were mostly related to mobility problems and limb-girdle weakness. Fifty-eight percent of the adult patients indicated the presence of mild muscular symptoms during childhood. Twenty-eight percent of the patients waited >5 years for the final diagnosis after the first visit to a physician for disease-related complaints. At the time of questionnaire completion, 48% of the study population used a wheelchair and 37% used artificial ventilation. Movements such as rising from an armchair, taking stairs or getting upright after bending over were difficult or impossible for more than two-thirds of the respondents. The age at onset, the rate of disease progression and the sequence of respiratory and skeletal muscle involvement varied substantially between patients. Seventy-six percent of the participants indicated being troubled by fatigue and 46% by pain. This survey has mapped the age at onset, presenting symptoms, heterogeneity in progression and range of disease severity in a large group of Dutch patients. We conclude that early manifestations in childhood require proper attention to prevent unnecessary delay of the diagnosis. The follow-up of patients with late-onset Pompe's disease should focus on respiratory and limb-girdle muscle function, the capacity to perform daily activities, and the presentation of fatigue and pain.
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PMID:Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. 1565 25


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