Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-four patients aged from one month to 16 years suffering from arterial stroke were carefully studied for any hereditary and acquired risk factors for stroke. No physiologic anticoagulant deficiency or antiphospholipid syndrome was found. Two patients had mitochondrial disease (MELAS). Six patients had migraineous stroke. Migraine and thrombotic disease in the families of the patients were not more prevalent than in the families of the controls. Preceding infections occurred in 34% of the patients, that is, significantly more common than in the age-matched controls. Two children had borreliosis. Repeat strokes occurred particularly in patients with migraine (n = 4) and MELAS (n = 2). The hereditary factors studied here seem to play only a minor role in pediatric patients. Repeated strokes have a varied etiology and are difficult to prevent. Important triggers of strokes are infections.
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PMID:Hereditary and acquired risk factors for childhood stroke. 788 30

Migraine and the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have some clinical features in common. First, cerebral infarctions, most often in the posterior cerebral regions, which are a main symptom of MELAS, may complicate migraine. Second, migrainous headache with vomiting is also a characteristic feature of the MELAS syndrome. Less frequently, hemicranial headache is present in another mitochondrial disease, myoclonic epilepsy with ragged-red fibers (MERRF). Moreover, there is a mild bias toward maternal transmission in migraine. Apart from clinical resemblance, there is some experimental evidence for mitochondrial dysfunction in migraine. There may be depression of respiratory chain enzyme activity in muscle and platelets, and magnetic resonance spectroscopy has revealed a defective energy metabolism in brain and muscle of migraine patients. There has not been a systematic study of mitochondrial DNA in migraine, however. We therefore analyzed the mitochondrial DNA in lymphocytes of 23 migraine patients with aura. Southern blot and polymerase chain reaction analysis of mitochondrial DNA failed to detect any large-scale deletions or point mutations at base pair 3243 (MELAS) and base pair 8344 (MERRF). Our data show that deletions of mitochondrial DNA and the most frequent point mutations of MELAS and MERRF syndromes are not common in migraine with aura. In particular, these data do not support the hypothesis that some cases of migraine may be monosymptomatic forms of a MELAS syndrome. We cannot exclude, however, that migraine may be associated with different point mutations of mitochondrial DNA or with mutations of autosomally coded respiratory chain subunit genes.
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PMID:Mitochondrial DNA in migraine with aura. 864 80

Congenital disorders of glycosylation (CDG) and mitochondrial diseases are multisystem disorders with clinical characteristics that may overlap. We present four patients with CDG whose phenotypes suggested the diagnosis of a mitochondrial disease. Patients 1 and 2 are siblings with hemiplegic headache, stroke-like episodes, lactic acidaemia and history of maternal migraine; their initial clinical diagnosis was MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes). Patient 3 suffers from ataxia, neuropathy, ophtalmoplegia and retinitis pigmentosa suggestive of NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. Patient 4 presented with neurological regression mimicking Leigh disease, with ptosis, myoclonus, ataxia and brainstem and cerebellar atrophy. Screening for mitochondrial disease including enzyme and mtDNA investigations on muscle biopsy were performed on Patients 1, 2 and 4 with normal results. However, evidence for a glycosylation disorder was substantiated by an increased carbohydrate deficient transferrin (CDT). The isoelectric focussing pattern of serum sialotransferrin was typical of CDG type I in Patients 1, 2 and 3 and was shifted towards the less sialylated bands in case 4. A deficiency of phosphomanomutase (PMM) confirmed the diagnosis of CDG-Ia in Patients 1, 2 and 3, who are compound heterozygous for mutations R141H/T237M (Patients 1 and 2) and R141H/P113L (Patient 3). In Patient 4, PMM activity was normal, and further enzymatic and molecular studies are underway. As the search for the primary defect in mitochondrial diseases is often unsuccessful, the pool of mitochondrial patients that remain without definite diagnosis might include CDG cases. Routine screening for CDG may avoid precocious invasive investigations.
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PMID:Congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking mitochondrial disease. 1158 67

Mitochondrial disorder is a relatively rare disease during childhood. Previous studies concluded that renal complications in this disease most often occur in patients with mitochondrial encephalomyopathies. We describe a boy with mitochondrial disease who presented with proteinuria while lacking neuromyopathy. Proteinuria was detected at the age of 6 years, including large amounts of low-molecular-weight proteins such as beta(2)- and alpha1-microglobulin. Renal functions were normal. Proximal tubular dysfunction and other renal manifestations were absent. Episodic neurologic problems such as migraine and nervous system diseases including epilepsy, depression, schizophrenia and amytrophic lateral sclerosis (ALS) were found in the boy's family members. Renal tubular basement membrane atrophy and interstitial fibrosis with mononuclear cell infiltration were observed. Ultrastructural examination showed mitochondria, mainly in the proximal tubules, which varied in size and had disoriented cristae. Mutation analysis using mitochondrial DNA (mtDNA) extracted from renal tissues demonstrated a A-->G point mutation at nucleotide position 3243 in the tRNA(Leu(UUR)) gene, while there was no mutation found in mtDNA extracted from peripheral leukocytes. Awareness among pediatricians of mitochondrial disorders, detection of low-molecular-weight proteinuria, renal ultrastructural examination and mutation analysis of mtDNA obtained from renal tissues could be important for early diagnosis of this disease.
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PMID:A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy. 1464 37

It is well recognized that headache, and especially migraine, runs in families. Recent studies into the heritability of primary headache subtypes, migraine, cluster and tension headache, and conditions in which headache is a prominent feature, such as the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and strokelike episodes, and the arteriopathy, cerebral autosomal-dominant arteriopathy with subcortical infarctions and leukoencephalopathy, are improving our understanding of the genetic contribution to headache. Studies of the rare familial hemiplegic migraine are leading to advances in understanding the pathophysiological mechanisms of the more common migraine types. Current knowledge of hereditary and genetic features of headache subtypes is reviewed and the implications for understanding the pathophysiology of migraine are discussed.
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PMID:Heredity, genes, and headache. 1704 52

Several hereditary disorders induce angiopathy in the intracranial cerebrovasculature and thus cause ischemic strokes. MELAS is a maternally inherited mitochondrial disorder that produces stroke-like events. Sickle cell disease, which is the result of a single base pair substitution, is a major cause of strokes in children. Homocystinuria, an autosomal recessive syndrome, produces premature atherosclerosis. Hereditary cerebroretinal vasculopathy is an autosomal dominant disorder that causes retinal and brain infarctions. Fabry disease is an x-linked disorder that can cause stroke in adults. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is an autosomal dominant syndrome that is associated with ischemic stroke and migraine-like headaches. The clinical presentation, stroke pathophysiology, and gene defects associated with these heritable disorders are reviewed.
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PMID:Mendelian and mitochondrial disorders associated with stroke. 1790 83

In single cases mitochondrial disorders may manifest as pancreatitis, but recurrent, chronic pancreatitis with exacerbations of at least 15 times without morphological alterations of the pancreas but concomitant diabetes mellitus has not been reported. In a 57-year-old Caucasian male mitochondrial disorder was diagnosed at the age of 49 years upon epilepsy with generalized and focal seizures, cognitive decline, migraine, mitochondrial myopathy, polyneuropathy, diabetes mellitus, hypokalie-mia, hyperlipidemia, atrial fibrillation, heart failure, sicca syndrome, recurrent pancreatitis, chronic diarrhea, polydipsia, hyperhidrosis, steatosis hepatis, anemia, thrombopenia, an abnormal lactate stress test, and a muscle biopsy showing ragged-red muscle fibers, single completely COX-negative fibers, target fibers, increased number of sarcoplasmatic lipid droplets, but normal mitochondrial morphology on electron microscopy. Between the age of 33 years and the age of 44 years, at least 15 episodes of pancreatitis, manifesting as severe abdominal pain, and elevated exocrine pancreatic enzymes, but without morphological alterations of the pancreas, responding well to H2-blockers and food restriction had occurred. Recurrent pancreatitis without morphological alterations of the pancreas may be a feature of multisystem mitochondrial disorder resulting in diabetes mellitus. Physicians should familiarize with pancreatitis as a manifestation of a mitochondrial disorder and mitochondrial disorder should be excluded in patients with pancreatitis.
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PMID:Recurrent pancreatitis as a manifestation of multisystem mitochondrial disorder. 1791 91

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.
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PMID:Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. 1899 Jan 25

Mitochondrial encephalomyopathy, lactacidosis and stroke-like episode (MELAS) syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder with a clinical onset between the first and third decade. The clinical hallmark is the stroke-like-episode, which mimicks ischemic stroke but is usually transient and non-disabling in nature. The morphological equivalent on MRI is a T2-hyperintensity, predominantly over the temporo-parieto-occipital region, not confined to a vascular territory, which is also hyperintense on diffusion weighted imaging and on apparent diffusion coefficient sequences (vasogenic edema, stroke-like lesion). Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes, or myopathy. Muscle biopsy typically shows ragged-red fibers, COX-negative fibers, SDH hyperreactivity, and abnormally shaped mitochondria with paracristalline inclusions. The diagnosis is confirmed by demonstration of a biochemical respiratory chain defect or one of the disease-causing mutations, of which 80 % affect the mitochondrial tRNALeu gene.
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PMID:[MELAS syndrome as a differential diagnosis of ischemic stroke]. 1901 24

Occipital stroke and occipital epilepsy are possible manifestations of mitochondrial diseases. A previous study in northern Finland suggested a frequency of 10% for mitochondrial disorder in young patients with stroke. Here we studied the epidemiology of occipital brain infarcts in a defined population in southwestern Finland. Patients diagnosed with brain infarct or visual field defect with onset at the ages of 18-45 years were identified from the discharge files at the Turku University Hospital. We further ascertained those patients with an occipital brain infarct in brain imaging or homonymous hemianopia with no signs of other etiology in brain imaging. We reviewed the clinical data for known stroke risk factors and analyzed samples for the m.3243A > G and m.8344A > G mutations in mitochondrial DNA (mtDNA), and determined mtDNA haplogroups and five common mutations in the gene encoding polymerase gamma (POLG1). Migraine was more common in young patients with occipital brain infarct than in the general population, especially among women. None of the patients harboured the m.3243A > G or m.8344A > G mutation in mtDNA or any of the five common mutations in POLG1. Interestingly, 17% of the men and 33% of the women belonged to the mtDNA haplogroup Uk, while its frequency in the general population is 17%. Our results suggest that mtDNA haplogroup Uk is associated with increased risk of occipital stroke in young women. POLG1 mutations have been associated with occipital epilepsy, but we did not find the common mutations in patients with occipital stroke.
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PMID:Epidemiology and characteristics of occipital brain infarcts in young adults in southwestern Finland. 1973 Sep 27


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