ABSTRACT
Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement.
Subject(s)
Axons/pathology , Cerebral Cortex/pathology , Leukoencephalopathies/complications , Spinal Diseases/complications , Amyloid beta-Protein Precursor/metabolism , Humans , Leukoencephalopathies/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Neurofilament Proteins/metabolism , alpha-Synuclein/metabolism , tau Proteins/metabolismABSTRACT
BACKGROUND: Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLA2, the gene encoding a ß subunit of succinate-CoA ligase, have been reported in 17 patients until now. Mutations in SUCLG1, encoding the α subunit of the enzyme, have been described in two pedigrees only. METHODS AND FINDINGS: In this study, two unrelated patients harbouring three novel pathogenic mutations in SUCLG1 were reported. The first patient had a severe disease at birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene expression system. The involvement of SUCLG1 was confirmed by western blot analysis, which showed absence of SUCLG1 protein in fibroblasts. The second patient has a milder phenotype, similar to that of patients with SUCLA2 mutations, and is still alive at 12 years of age. Western blot analysis showed some residual SUCLG1 protein in patient's fibroblasts. CONCLUSIONS: Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2-like phenotype is found in patients with residual SUCLG1 protein. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.
Subject(s)
Methylmalonic Acid/urine , Mitochondrial Encephalomyopathies/genetics , Mitochondrial Encephalomyopathies/physiopathology , Mutation , Severity of Illness Index , Succinate-CoA Ligases/genetics , Amino Acid Sequence , Child , Fatal Outcome , Humans , Infant , Male , Methylmalonic Acid/blood , Mitochondrial Encephalomyopathies/mortality , Models, Molecular , Molecular Sequence Data , Mutation, Missense , Phenotype , Succinate-CoA Ligases/chemistry , Succinate-CoA Ligases/deficiency , Succinate-CoA Ligases/metabolismABSTRACT
INTRODUCTION: Pompe's disease, also called glycogen storage disease type II or acid maltase deficiency, is an autosomal recessive disease caused by an enzymatic deficiency of acid-alpha-glucosidase (GAA). This deficiency causes an accumulation of intralysosomal glycogen in different organs. The classic form appears in the newborn with a very severe hypotonia and cardiomyopathy, which lead to death before age two. Less frequently, the disease appears only in childhood or in adult life, so called late-onset Pompe's disease. This form causes a very progressive limb-girdle myopathy and restrictive respiratory failure. The diagnosis is based on a low level of GAA either in the muscle biopsy or in the leucocytes. We report six cases of late-onset Pompe's disease from the Languedoc-Roussillon district. METHOD: Our work was a retrospective analysis of all cases of Pompe disease diagnosed in adults between 1975 and 2006 at the Montpellier and Nîmes University Hospital. We describe the clinical presentation and course of this form and explain the diagnostic approach. Results. The mean age at onset was 44.3 years (range: 36-60 years). The first symptom was fatigability (50%), gait difficulty (50%) and dyspnea (16%). The mean delay from symptom onset to diagnosis was 8.4 years (range: 17 years). Fatal outcome due to respiratory failure was noted in three patients. The mean time between symptom onset and death (four patients) was 20.75 years (range: 37 years). The diagnosis was made on the muscle biopsy showing a low level of GAA. Muscle was strictly normal on the morphologic study in one patient, pointing out the requirement for enzymatic analysis. Molecular confirmation was available in one patient. DISCUSSION: Late-onset Pompe's disease is a possible cause of limb-girdle myopathy. Respiratory involvement is a characteristic feature. Enzymatic assay of GAA activity on the muscle biopsy is required for certain diagnosis. CONCLUSION: It is very important to recognize the adult form of Pompe's disease, a possible cause of limb-girdle myopathy, in order to search for respiratory failure and propose non-invasive ventilation if necessary. Moreover, substitutive therapy (recombinant acid-alpha-glucosidase) has shown efficiency for the classical infantile form of Pompe's disease and such treatment could be proposed for the adult form if larger studies confirm its efficacy.
Subject(s)
Glycogen Storage Disease Type II/pathology , Adult , Age of Onset , Biopsy , Disease Progression , Dyspnea/etiology , Dyspnea/physiopathology , Female , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Glycogen Storage Disease Type II/diagnosis , Humans , Male , Middle Aged , Muscle Fatigue/physiology , Muscles/pathology , Respiratory Insufficiency/etiology , Retrospective Studies , alpha-Glucosidases/metabolismABSTRACT
CONTEXT: Progressive supranuclear palsy (PSP) is classically characterized by supranuclear ophthalmoplegia, paroxysmal imbalance with backward falling, axial dystonia, rigidity, pseudobulbar palsy and cognitive dysfunction. However, incomplete or atypical clinical presentation has been previously reported, but in all these cases, the patients had at least one of the main clinical features of the disease (ophthalmoplegia, parkinsonian syndrome or cognitive dysfunction). CASE REPORT: A 60-year-old woman presented with nocturnal agitation and choreiform movements. A few months later she developed severe swallowing disorders, caused by achalasia of the upper esophageal sphincter, and responsible for recurrent acute respiratory distress and pneumonia, prevailing to tracheotomy and gastrostomy. She died suddenly two years after the onset of the symptoms. RESULTS: Postmortem examination of brain revealed a tauopathy, with deposition of abnormal phosphorylated tau in threads and in coiled-shaped as well as globose tangles in the brainstem, subthalamic nuclei and hippocampus. Nuclei of the medulla, including the vagus/solitarius complex and the region of the nucleus ambiguous were especially rich in tau positive inclusions. Ultrastructural analysis of globoid-shaped tangles in the brainstem revealed the presence of straight and paired helicoidal filaments compatible with a PSP. CONCLUSIONS: This case contributes to improve knowledge of the clinical phenotypic range of PSP. In this case, the neuropathological lesions accounted for most of the symptoms. However, the early death of the patient was probably related to the particular distribution of the neuropathological lesions. This case suggests that the initial neuropathological changes in PSP is located in the dorsal brainstem.
Subject(s)
Chorea/pathology , Esophageal Achalasia/pathology , Sleep Wake Disorders/pathology , Supranuclear Palsy, Progressive/pathology , Chorea/complications , Deglutition Disorders/etiology , Diagnosis, Differential , Esophageal Achalasia/complications , Esophageal Achalasia/diagnostic imaging , Female , Humans , Hypoglossal Nerve/pathology , Inclusion Bodies/pathology , Middle Aged , Radiography , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/surgery , Sleep Wake Disorders/complications , Substantia Nigra/pathology , Supranuclear Palsy, Progressive/diagnosis , TracheostomyABSTRACT
Mutations of mitochondrial genome are responsible for respiratory chain defects in numerous patients. We have used a strategy, based on the use of a mismatch-specific DNA endonuclease named " Surveyor Nuclease", for screening the entire mtDNA in a group of 50 patients with neuromuscular features, suggesting a respiratory chain dysfunction. We identified mtDNA mutations in 20% of patients (10/50). Among the identified mutations, four are not found in any mitochondrial database and have not been reported previously. We also confirm that mtDNA polymorphisms are frequently found in a heteroplasmic state (15 different polymorphisms were identified among which five were novel).
Subject(s)
DNA, Mitochondrial/genetics , Endonucleases , Genetic Testing/methods , Neuromuscular Diseases/genetics , Adolescent , Adult , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Mitochondrial Diseases/genetics , PedigreeABSTRACT
INTRODUCTION: The most frequent acute and sub-acute complications of chronic alcoholism are delirium tremens, hepatic encephalopathy and Gayet-Wernicke encephalopathy. Morel laminar sclerosis is a rare and less known complication, often reported with Marchiafava-Bignami disease. CASE REPORT: A 57-year-old alcoholic man presented delirium after surgery. Anterograde and retrograde amnesia as well as wrong recognitions appeared progressively and one generalized seizure occurred. He then developed mutism and became bedridden. Magnetic resonance imaging (MRI) showed high-intensity bilateral temporoparietal signals from white matter on T2-weighted images and high-intensity signals from the parietal cortex on T1-weighted images. The patient died four months after the onset of the delirium. Post-mortem examination of the brain showed cortical laminar necrosis with Alzheimer Type II gliosis but without demyelinisation of the corpus callosum. CONCLUSION: Cortical laminar necrosis with chronic ethylism is usually called Morel's laminar sclerosis. Nevertheless, histology is not typical of this diagnosis, because of necrosis especially of the second (and not the third) layer of the cortex, and because of the absence of lesion of the corpus callosum. MRI data are of interest here because they were rarely reported in cases of Morel's laminar sclerosis.
Subject(s)
Amnesia/etiology , Brain/pathology , Cerebral Cortex/pathology , Postoperative Complications/pathology , Delirium/etiology , Hernia, Umbilical/complications , Humans , Hypoxia, Brain/pathology , Magnetic Resonance Imaging , Male , Middle Aged , NecrosisABSTRACT
Among neuroeosinophilic syndromes, neuromuscular disorders are considered as a special group, including perimyosistis, polymyositis and fasciitis. These three disorders are considered as a continuum. They usually without a recognized cause, and are considered to be spontaneous or exercise-induced. We report the case of a 43 year-old woman who experienced angioedema followed by an histologically proven-fasciitis with eosinophilia after Ramipril (Triatec) use. Causal attribution to Ramipril was considered "plausible". To our knowledge this side effect has never been reported with this drug.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/adverse effects , Eosinophilia/chemically induced , Fasciitis/chemically induced , Ramipril/adverse effects , Adult , Angioedema/chemically induced , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Drug Eruptions/etiology , Female , Humans , Hypertension/drug therapy , Hypertension/etiology , Obesity/complications , Ramipril/therapeutic useABSTRACT
OBJECTIVE: Statins (3-hydroxymethylglutaryl-coenzyme A reductase inhibitor) are widely used to treat hypercholesterolemia. They are generally well tolerated, but myotoxic effects have been reported and the corresponding mechanisms are still a matter of debate. The aim of the present study was to determine whether impairment of calcium homeostasis and/or mitochondrial impairment could account for the adverse effects of statins in skeletal muscle. METHODS: Eleven patients with increased creatine kinase levels and myalgias after statin treatment were evaluated using in vitro contracture tests (IVCTs), histology, and 31P magnetic resonance spectroscopy (31P-MRS). RESULTS: IVCT results were abnormal in 7 of the 9 patients, indicating an impaired calcium homeostasis. The 31P-MRS investigation disclosed no anomaly at rest, and the aerobic function assessed during the postexercise recovery period was normal. On the contrary, the pH recovery kinetics was significantly slowed down as indicated by a reduced proton efflux, which could be ultimately linked to a failure of calcium homeostasis. Overall, our observations indicate a normal mitochondrial function and raise the possibility that statins may unmask a latent pathology involving an impairment of calcium homeostasis such as malignant hyperthermia (MH). CONCLUSION: In case of susceptibility to MH, statins treatment must be administered with caution, and signs of adverse effects should be checked.
Subject(s)
Creatine Kinase/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Muscle, Skeletal/metabolism , Aged , Biopsy , Calcium/metabolism , Female , Humans , Hypercholesterolemia/drug therapy , Magnetic Resonance Spectroscopy , Male , Middle Aged , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscular Diseases/chemically induced , Muscular Diseases/pathology , PainABSTRACT
The authors analyzed muscle biopsy specimens of 104 patients with creatine kinase activity greater than 500 UI/L (normal 10 to 170 UI/L) without signs of muscle weakness. They achieved a definite or probable diagnosis in 55% of cases. The most frequently identified diseases were glycogen storage diseases, muscular dystrophies, and inflammatory myopathies. The probability of making a diagnosis was higher in children and when creatine kinase level was greater than 2,000 UI/L.
Subject(s)
Creatine Kinase, MM Form/blood , Neuromuscular Diseases/blood , Adolescent , Adult , Aged , Biomarkers , Biopsy , Child , Child, Preschool , Cohort Studies , Dystrophin/deficiency , Fatigue/blood , Fatigue/etiology , Female , Glycogen Storage Disease Type II/blood , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type V/blood , Glycogen Storage Disease Type V/diagnosis , Humans , Male , Middle Aged , Muscle Cramp/blood , Muscle Cramp/etiology , Muscle, Skeletal/enzymology , Muscle, Skeletal/pathology , Neuromuscular Diseases/diagnosis , Retrospective StudiesABSTRACT
We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.
Subject(s)
Muscular Diseases/congenital , Muscular Diseases/genetics , Myopathies, Nemaline/diagnosis , Myopathies, Nemaline/genetics , Actins/genetics , Adolescent , Adult , Biopsy , Child, Preschool , Female , Humans , Male , Muscles/pathology , Muscular Diseases/diagnosis , Mutation , Myosin Heavy Chains/genetics , PedigreeABSTRACT
Leigh syndrome is a heterogeneous disorder, usually due to a defect in oxidative metabolism. Mutations in SURF1 gene have been identified in patients with cytochrome c oxidase deficiency. We report a homozygous splice site deletion [516-2_516-1delAG] in a young girl presenting with cytochrome c oxidase-deficient Leigh syndrome. Identification of molecular defect is indispensable for genetic counselling and prenatal diagnosis.
Subject(s)
Cytochrome-c Oxidase Deficiency/genetics , Leigh Disease/genetics , Mutation , Proteins/genetics , Female , Homozygote , Humans , Infant , Membrane Proteins , Mitochondrial ProteinsABSTRACT
The idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterized by chronic lymphocytic and macrophagic infiltration in muscle. Because the mechanism for recruitment of these cells probably involves chemokines, we focused on the study of the expression pattern of some beta chemokines and receptors because it may provide a basis for selective immunotherapy. The expression of CCL3 (MIP-1alpha), CCL4 (MIP-1beta), CCL5 (RANTES) and their main receptors (CCR1 and CCR5) was studied by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry in a series of 16 IIM and five controls (four normal muscles and one tonsil). Except for CCL5, strong expression was observed by RT-PCR with all molecules in all IIM subtypes in comparison to control muscle. Immunohistochemistry revealed diffuse CCL4 expression in all vessels in dermatomyositis. In both polymyositis and sporadic inclusion body myositis (s-IBM) it was restricted to vessels in the vicinity of inflammatory exudates. CCL5 expression was low, restricted to a few inflammatory cells in all IIM; CCR1 expression was mainly restricted to macrophages and s-IBM endothelial cells, whereas CCR5 was localized in inflammatory cells invading non-necrotic muscle fibres. Expressions of both receptors were also recorded in few muscle fibres. In conclusion, the upregulation of beta chemokines and receptors in IIM and their differential expression by various cells may contribute to chronic inflammation and to the peculiar distribution of inflammatory exudates in these diseases.
Subject(s)
Chemokines, CC/biosynthesis , Muscle, Skeletal/metabolism , Myositis/metabolism , Receptors, Chemokine/biosynthesis , Adolescent , Adult , Aged , Female , Humans , Immunohistochemistry , Male , Middle Aged , Muscle, Skeletal/pathology , Myositis/pathology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Sporadic inclusion body myositis (s-IBM) is the most frequent progressive acquired inflammatory myopathy in people older than 50 years. Abnormal aggregates of 'Alzheimer's proteins', including tau proteins, have been previously demonstrated in s-IBM. In the present study, we have investigated by immunohistochemistry and immunoblotting analysis the presence of tau proteins in muscle biopsy samples from patients with s-IBM and other myopathies with rimmed vacuoles, using newly developed antibodies raised against tau protein epitopes found in Alzheimer's disease brain. Tau immunoreactivity was shown in rimmed vacuoles or inclusions, preferentially with antibodies directed against phosphorylated carboxy-terminal epitopes of tau proteins. Cytoplasmic reactivity was also demonstrated in atrophic, nonvacuolated fibres, as well as in non-necrotic fibres invaded by inflammatory cells. Abnormally phosphorylated tau aggregates were also found in other compartments of the muscle fibre in s-IBM and other myopathies. Tau immunoblotting showed an electrophorectic profile of a doublet within the range of 60-62 kDa isovariants, which was different from tauopathies of the central nervous system. Finally, the unique pattern of immunoreactivity of s-IBM samples towards anti-tau antibodies is a new clue to a possible distinct subclass of peripheral tauopathy, different from the tauopathies of the central nervous system.
Subject(s)
Myositis, Inclusion Body/metabolism , tau Proteins/metabolism , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal , Blotting, Western , Child, Preschool , Female , Humans , Immunoblotting , Immunoelectrophoresis , Immunohistochemistry , Infant , Male , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Myositis, Inclusion Body/pathology , Phosphorylation , Vacuoles/metabolism , Vacuoles/pathologyABSTRACT
Andersen syndrome includes a clinical triad with periodic paralysis, cardiac arrhythmia and dysmorphic features most often mild but relevant. It is a potassium channelopathy due to mutation of KCJN2 gene coding for Kir 2.1 protein. We report a familial case with mutation R218W of Kir 2.1 and discuss the main phenotypic and genetic aspects of Andersen syndrome. Muscle manifestations are essentially a periodic paralysis most often of hypokaliemic type. Muscle biopsy reveals tubular aggregates but can be normal as it is shown in the same patient in our kindred. Our proband complained of paralytic attacks since childhood and at adult age she demonstrated a mild permanent deficit of pelvic girdle muscles as it has been described in other types of periodic paralysis after a long duration course. Cardiac manifestations may include in a variable manner a long QT syndrome, premature ventricular contractions, complex ventricular ectopy, polymorphic or bidirectional ventricular tachycardia. Imipramine had a positive effect on arrhythmia in our case. Dysmorphic features are often mild and have to be cautiously looked for as a clue to the diagnosis of Andersen syndrome. They can be easily overlooked if not systematically looked for. Clinical expressivity is variable including in the same family. In our observation, the daughter showed a complete triad, early expressed, which allowed the diagnosis. Her father was late diagnosed on ventricular dysrhytmia but without muscle manifestations and dysmorphic features. Since KCJN2 gene mutation identification, locus heterogeneity of Andersen syndrome was shown. Andersen syndrome kindreds without mutations in KCNJ2 were clinically indistinguishable from KCNJ2-associated subjects. KCNJ2 gene encodes the inward rectifier K+ channel Kir2.1 which plays an important role in maintaining membrane potential and during the terminal phase of cardiac action potential repolarization. Several studies showed a dominant negative effect of the mutation on Kir 2.1 channel function.
Subject(s)
Arrhythmias, Cardiac/physiopathology , Glycogen Storage Disease Type IV/physiopathology , Paralysis/physiopathology , Adolescent , Electrocardiography , Facial Bones/abnormalities , Female , Glycogen Storage Disease Type IV/diagnosis , Glycogen Storage Disease Type IV/genetics , Humans , Male , Membrane Potentials/physiology , Middle Aged , Potassium Channels/geneticsABSTRACT
We carried out a retrospective study of 352 medical terminations of pregnancy (MTP) carried out in a large French administrative region over two consecutive years. We analysed the indications for MTP and then compared the prenatal ultrasound diagnosis with fetal autopsy findings in order to demonstrate the value of pathological examination of the fetus in prenatal diagnosis and genetic counselling as well as the need to check by autopsy the quality of ultrasound screening. Preliminary analysis of the indication for these MTP showed that in 69.9% ultrasound screening had been carried out, revealing mainly brain abnormalities (22.2%) and heart defects generally associated with chromosomal abnormalities (32.1%). Prenatal findings were in agreement with autopsy results, showing no false-positive prenatal diagnoses. However, in 7.9% of cases in which brain abnormalities were detected, confirmation was not possible at autopsy because of tissue autolysis, showing the need for optimal conditions of expulsion. In 35.8% of cases, confirmation of the diagnosis by autopsy was not useful for management but still added to medical knowledge and demonstrated to the mother the reality of the defects. In 50.9%, the autopsy findings were decisive for genetic counselling.
Subject(s)
Aborted Fetus/pathology , Abortion, Induced , Adolescent , Adult , Autopsy , Chromosome Aberrations , Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/genetics , Female , France , Genetic Predisposition to Disease , Humans , Middle Aged , Pregnancy , Pregnancy Complications , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
OBJECTIVE: To evaluate the prevalence and clinical consequences of gastro-intestinal manifestations in Maternally Inherited Diabetes and Deafness syndrome (MIDD). METHODS: We report the case of fatal intestinal pseudo-obstruction in a patient with severe MIDD. Using a standardized questionnaire, we evaluate the frequency of gastrointestinal tract (GIT) symptoms in 10 patients with MIDD (8 A3243G and 2 T14709C mutations of mitochondrial DNA). The reference population consisted of 50 patients with type 1 diabetes matched for disease duration. In 4 patients with digestive manifestations endoscopic examination of upper and lower GIT was performed allowing multiple biopsies for ultrastructural and molecular analysis. RESULTS: GIT symptoms were frequently reported in MIDD specially in patients bearing the mt 3243 mutation. The manifestations i.e. constipation, diarrhea or both, were more frequent in this subgroup than in type 1 diabetic population (88% vs 28%, p<0.05). Ileus is a rare and severe complication with a frequent fatal Issue. Ultrastructural analysis of the mucosa from oesophagus, stomach, duodenum, colon and rectum showed mild modifications such as accumulation of normal mitochondria and lipId droplets. Heteroplasmy levels were determined in 4 patients harboring the 3243 mutation. In three patients the percentage of mutated DNA increased from upper to lower GIT. CONCLUSIONS: Gastrointestinal symptoms are frequent in MIDD secondary to 3243 mutation. They might explain the lower body weight observed in these patients in comparison to reference diabetic populations. They can also lead to a severe complication namely the intestinal pseudo-obstruction.
Subject(s)
DNA, Mitochondrial/genetics , Deafness/genetics , Diabetes Mellitus/genetics , Diabetes Mellitus/physiopathology , Gastrointestinal Diseases/epidemiology , Mutation, Missense , Constipation/epidemiology , Constipation/genetics , Deafness/complications , Deafness/physiopathology , Diabetes Complications , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/physiopathology , Diarrhea/genetics , Digestive System/pathology , Female , Gastrointestinal Diseases/genetics , HumansABSTRACT
This study is to further confirm the diagnostic value of class I MHC detection in muscle biopsies of adult patients presenting with clinical features of dermatomyositis (DM) and to address its diagnostic value in the case of nonspecific biopsies. A retrospective study was performed on muscle biopsies in 22 patients presenting with clinical features of DM. Immunohistochemical detection of class I MHC was performed in all cases. On pathological features two groups of patients were recorded: group I (14 patients) with typical features of DM and group II (eight patients) with almost normal muscle biopsies (no inflammatory exudates, no perifascicular atrophy). Abnormal sarcolemmal class I MHC expression was recorded in all cases. In all muscle biopsies of group I patients, class I MHC expression was observed in almost all fibres but was stronger in perifascicular areas (eight patients) or was restricted to perifascicular atrophic fibres (six patients). In all muscle biopsies of group II patients, only some perifascicular fibres expressed class I MHC. According to Bohan and Peter criteria, patients were classified as definite DM (nine group I and three group II patients), probable DM (five group I and two group II patients) and possible DM (three group II patients). Abnormal perifascicular class I MHC expression is of diagnostic value in patients presenting with clinical features of DM especially when muscle biopsy fails to show typical features such as inflammatory infiltrates and/or perifascicular atrophy.
Subject(s)
Dermatomyositis/diagnosis , Histocompatibility Antigens Class I/metabolism , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Adult , Aged , Biomarkers/analysis , Biopsy , Dermatomyositis/metabolism , Dermatomyositis/physiopathology , Electromyography , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron , Middle Aged , Muscle, Skeletal/ultrastructure , Retrospective StudiesABSTRACT
The authors report a 71-year-old woman with limb-girdle muscular dystrophy (LGMD) associated with an R27Q mutation in the CAV3 gene. Immunohistochemistry showed a >90% reduction of caveolin-3 on the sarcolemma by western blot, and anti-dysferlin immunoreactivity was reduced. This case emphasizes that an R27Q missense mutation in the CAV3 gene can lead to various clinical phenotypes including hyperCKemia, rippling muscle disease, distal myopathy, and LGMD1C.