ABSTRACT
The aim of this study was to evaluate the diagnostic performance of Simtomax® CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys® Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92 % (95 % confidence interval [95 %CI]: 79-97), specificity 97 % (95 % CI: 91-99 %), PPV 94 % (95 % CI: 81-98) and the NPV 96 % (95 % CI: 89-99). When considering only samples collected ≥ 15 days post-symptoms (DPS), the sensitivity increased to 98 % (95 %CI: 86-100) and the specificity was 97 % (95 % CI: 91-99 %). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days.
Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/standards , COVID-19/diagnosis , Immunoassay/standards , Reagent Kits, Diagnostic/standards , Adolescent , Adult , COVID-19/immunology , COVID-19 Serological Testing/methods , Female , Humans , Immunoassay/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , SARS-CoV-2/immunology , Sensitivity and Specificity , Young AdultABSTRACT
The nucleosome remodeling deacetylase (NuRD) complex is a highly conserved regulator of chromatin structure and transcription. Structural studies have shed light on this and other chromatin modifying machines, but much less is known about how they assemble and whether stable and functional sub-modules exist that retain enzymatic activity. Purification of the endogenous Drosophila NuRD complex shows that it consists of a stable core of subunits, while others, in particular the chromatin remodeler CHD4, associate transiently. To dissect the assembly and activity of NuRD, we systematically produced all possible combinations of different components using the MultiBac system, and determined their activity and biophysical properties. We carried out single-molecule imaging of CHD4 in live mouse embryonic stem cells, in the presence and absence of one of core components (MBD3), to show how the core deacetylase and chromatin-remodeling sub-modules associate in vivo. Our experiments suggest a pathway for the assembly of NuRD via preformed and active sub-modules. These retain enzymatic activity and are present in both the nucleus and the cytosol, an outcome with important implications for understanding NuRD function.
Subject(s)
Histone Deacetylases/metabolism , Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism , Nucleosomes/metabolism , Animals , Cell Nucleus/metabolism , Chromatin/metabolism , Chromatin Assembly and Disassembly/physiology , Cytosol/metabolism , Drosophila/metabolism , Mice , Protein Subunits/metabolism , Stem Cells/metabolismABSTRACT
Objetivo La inmunoglobulina específica frente a citomegalovirus ha demostrado su eficacia en la prevención y tratamiento de la infección en el trasplante de órganos sólidos. Distintos estudios indican una eficacia similar respecto a las presentaciones de Ig inespecíficas. El objetivo de este estudio es determinar la titulación de inmunoglobulina anti-citomegalovirus de una de las presentaciones de inmunoglobulinas inespecíficas autorizadas en España. Método Estudio observacional en el que se analizó la titulación de anticuerpos anti-citomegalovirus de distintos lotes de Flebogamma® 5% 5g utilizados en el Hospital Universitari Vall dHebron durante los años 2008 y 2009.ResultadosSe analizaron 27 lotes, que incluyeron 18.944 viales de Flebogamma® 5%. En función del origen, la concentración mediana de inmunoglobulina anti-citomegalovirus fue de 28UPEI/ml y 22UPEI/ml para los viales de origen norteamericano y español, respectivamente (IC 95 % para la diferencia de las medianas de 5 a 6UPEI/ml; p<0 001ConclusionesLa concentración de anticuerpos anti-citomegalovirus de los lotes de inmunoglobulina inespecífica analizados es ligeramente inferior respecto a las especialidades de inmunoglobulinas específicas. Estas diferencias pueden compensarse mediante un ajuste posológico (AU)
Objective Specific immunoglobulin against cytomegalovirus has demonstrated its effectiveness in preventing and treating infections in solid organ transplantation. Several studies indicate that non-specific immunoglobulin is just as effective. This study aims to determine anti-cytomegalovirus immunoglobulin titres from one of the non-specific immunoglobulin presentations authorised in Spain. Method This was an observational study, in which we analysed the anti-cytomegalovirus antibody titres from different batches of Flebogamma® 5% 5g used at the Hospital Universitari Vall d'Hebron during 2008 and 2009.ResultsWe analysed 27 batches, which included 18,944 vials of Flebogamma® 5%. Depending on the origin, the median concentration of anti-cytomegalovirus immunoglobulin was 28PEI-U/ml and 22PEI-U/ml per vial of North American and Spanish origin, respectively (CI 95% for the difference of the medians 5 to 6PEI-U/ml; p<0 001ConclusionsThe anti-cytomegalovirus antibody concentration of the non-specific immunoglobulin batches analysed was slightly lower than in the specific immunoglobulin preparations. These differences can be compensated by adjusting the dosage (AU)
Subject(s)
Humans , Immunoglobulins/isolation & purification , Cytomegalovirus/isolation & purification , Organ Transplantation/adverse effects , Biomarkers/analysis , Risk FactorsABSTRACT
Proton magnetic resonance spectroscopic imaging ((1) H-MRSI) has been advocated as a valuable tool for prostate cancer diagnosis. However, a barrier to widespread clinical use of this technique is the lack of robust quantification methods that yield reproducible results in an institution-independent manner. The main goal of this study was to develop a standardized and fully automated approach (LCModel-based) for quantitative prostate (1) H-MRSI. To this end, a dedicated basis set was constructed by the combination of simulated (citrate, Cit; choline, Cho, and creatine, CR) and experimentally acquired (spermine, Spm) spectra. The overlapping Spm, Cho, and Cr could be resolved and quantified individually, thus allowing for the independent assessment of glandular (Cit and Spm) and proliferative (Cho) components. Several metabolite ratios were calculated and compared to the histologic findings of prostatectomy specimens from 10 prostate cancer patients with Gleason scores (3 + 3) and (3 + 4). The Cho mole fraction and the Cho/(Cit + Spm) ratio were found to best discriminate between prostate cancer and healthy tissue. The comparison between the quantitative MRSI results and the histologic findings suggests that no correlation exists between the detected metabolic alterations and the Gleason score of low-grade tumors.
Subject(s)
Adenocarcinoma/metabolism , Magnetic Resonance Spectroscopy , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Adenocarcinoma/pathology , Choline/analysis , Citric Acid/analysis , Creatine/analysis , Humans , In Vitro Techniques , Male , Phantoms, Imaging , Spermine/analysisABSTRACT
OBJECTIVE: Specific immunoglobulin against cytomegalovirus has demonstrated its effectiveness in preventing and treating infections in solid organ transplantation. Several studies indicate that non-specific immunoglobulin is just as effective. This study aims to determine anti-cytomegalovirus immunoglobulin titres from one of the non-specific immunoglobulin presentations authorised in Spain. METHOD: This was an observational study, in which we analysed the anti-cytomegalovirus antibody titres from different batches of Flebogamma(®) 5% 5g used at the Hospital Universitari Vall d'Hebron during 2008 and 2009. RESULTS: We analysed 27 batches, which included 18,944 vials of Flebogamma(®) 5%. Depending on the origin, the median concentration of anti-cytomegalovirus immunoglobulin was 28PEI-U/ml and 22PEI-U/ml per vial of North American and Spanish origin, respectively (CI 95% for the difference of the medians 5 to 6PEI-U/ml; p<0.001). CONCLUSIONS: The anti-cytomegalovirus antibody concentration of the non-specific immunoglobulin batches analysed was slightly lower than in the specific immunoglobulin preparations. These differences can be compensated by adjusting the dosage.
Subject(s)
Cytomegalovirus Infections/drug therapy , Cytomegalovirus/immunology , Immunoglobulins/blood , Immunoglobulins/therapeutic use , Cross-Sectional Studies , Humans , Retrospective StudiesABSTRACT
INTRODUCTION: Advances in neuroimaging in the last decade have allowed a number of new findings about attention deficit hyperactivity disorder (ADHD) to be obtained. Quickly developing technology, together with the progress being made in genetics and neurochemical research, suggests a dysfunction of the fronto striatal circuit that involves the prefrontal cortex and its relationship with the basal, thalamic and cerebellar nuclei as the pathophysiological foundation of this disorder. On the other hand, neuroimaging in the future may complement clinical evaluation, which will favour more accurate diagnoses and allow the subtypes and even the mode of treatment and its monitoring to be identified. AIMS AND DEVELOPMENT: The aim of this study was to review the more significant literature on neuroimaging and ADHD and to discuss the usefulness and drawbacks of the different modes of neuroimaging techniques that can be applied with a view to gaining an improved and deeper knowledge of ADHD in the future. CONCLUSIONS: Although the development of neuroimaging in ADHD is a promising area, at the present time its diagnostic value is very restricted. One of the greatest difficulties in this respect concerns the clinical, genetic and pathophysiological heterogeneity of the disorder. Hence, given the inexistence of a specific marker, future studies will have to search for several markers that have a suitable value in the diagnosis, prognosis and/or treatment of the different subtypes of ADHD.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Brain , Diagnostic Imaging , Attention Deficit Disorder with Hyperactivity/pathology , Attention Deficit Disorder with Hyperactivity/physiopathology , Brain/pathology , Brain/physiopathology , Brain Mapping , Humans , Magnetic Resonance Imaging , Positron-Emission Tomography , Tomography, Emission-Computed, Single-PhotonSubject(s)
Catheter Ablation/methods , Cecal Neoplasms , Colorectal Neoplasms , Laparoscopy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Aged , Humans , MaleABSTRACT
PATIENTS AND METHODS: From a series of 530 patients with neurofibromatosis type 1 (NF1), we performed a retrospective assessment of the long-term neurologic, visual, neuroimaging and evolution of 80 patients (15%) with optic pathway gliomas (OPG). All the 80 patients, 58 (72.5%) females and 22 (27.5%) males were diagnosed during childhood (below age 16 years), range 13 months to 15 years (average: 4.6 years). RESULTS: Image studies showed the distribution of the lesions among optic nerves, chiasm, tracts and radiations demonstrated that only 25% of the tumors involved only one optic nerve and 11.5% were located only in the chiasm, while 40% involved one or both optic nerves and chiasm, tracts and radiations. Two patients showed pilocytic astrocytoma in the histological study. Late diagnosis (after 7 years of age) of OPG was made in three patients and late progression was evident in three others who required surgical resection, radiotherapy or chemotherapy. CONCLUSIONS: All patients were diagnosed during childhood (below 16 years of age). Incidence was double in girls than in boys. Despite the apparent tumoral agressivity of the magnetic resonance and magnetic resonance spectroscopy images, histological findings corresponded to benign pilocytic astrocytoma. Some tumors follow the growth after 7 years. Continued monitoring of patients with NF1 into adulthood is advisable.
Subject(s)
Neoplasms, Multiple Primary/diagnosis , Neurofibromatosis 1/diagnosis , Optic Nerve Glioma/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Retrospective StudiesABSTRACT
OBJECTIVE: To describe the clinical and imaging findings of 20 patients (12 women and 8 men) with brain stem tumors associated with neurofibromatosis type 1 (NF1). PATIENTS AND METHODS: All patients were first time studied before 11 years old. Clinical and magnetic resonance (MR) study were made in all 20 patients, and spectroscopic MR (SMR) was performed in 7 patients. Thirteen of the 20 patients (65 %) also had optic pathway tumor. Brain stem tumor identification occurred at the same time as NF1 in the patients who were studied by MR at the time of the first consult. RESULTS: Brain stem identification occurred at the same time as that of the NF1 in patients who were studied by MR from the beginning. Diffuse or localized medullary enlargement was the most frequent MR imaging and appeared in 13 patients (65%), followed by the tumor that involved all brain stem (pontine and medullary areas) that appeared in 6 patients (30 %). In the last group, one tumor showed extension through brain stem and medial cerebellar parts, another was located in the aqueduct and in the periaqueductal areas and showed slow progressive growth, and one third patient had a tumor with aggressive signs in the SMR study. Another patient had an aggressive tumor that involved the left optic nerve, chiasm, mesencephalon and upper right pontine areas. The histological study of the tumoral biopsic tissue of the two last patients showed astrocitoma degree 1 (benign tumor). The two aggressive tumors were treated with radiotheraphy and chemotherapy and they are still alive 4 and 7 years respectively after treatment. Three patients who had aqueductal obstruction and hydrocephalus were treated with shunt. The rest of patients did not receive treatment. Only one of the 20 patients died, although it was due to a malignant chiasmatic tumor, that had been treated twenty years before, and not by the brain stem tumor. CONCLUSIONS: In NF1, brain stem tumors are the most frequent tumors of the posterior fossa and the second most frequent of the central nervous system (CNS). MR and SMR are necessary to a correct identification of the tumor in some patients. Most of these tumors are benign.
Subject(s)
Brain Neoplasms/complications , Brain Neoplasms/diagnosis , Brain Stem , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Neurofibromatosis 1/complications , Child , Child, Preschool , Female , Humans , Infant , MaleABSTRACT
Inbreeding depression has been observed in most fruit trees, negatively affecting the offspring of related parents. This problem is steadily increasing due to the repeated utilization of parents in breeding programmes. In almond, self-compatibility transmission from 'Tuono' to its offspring remains partially unexplained due to deviations from the expected genotype ratios. In order to test if these deviations could be due to inbreeding, the S-genotypes of the seedlings of four almond families, 'Tuono' (S(1)S(f )) x 'Ferragnès' (S(1)S(3)), 'Tuono' (S(1)S(f)) x 'Ferralise' (S(1)S(3)) and reciprocal crosses were studied. The S-genotype determination of each seedling by separation of stylar S-RNases and by S-allele-specific PCR amplification gave identical results. The ratio of S-genotypes of the family 'Tuono' x 'Ferralise' was the one least adjusted to the expected 1:1 ratio, because the number of self-compatible seedlings (S(f)S(3)) was less than a half the number of self-incompatible ones (S(1)S(3)). A mechanism acting against inbreeding would favour cross-breeding in the following generation to increase heterozygosity. This fact stresses the need to avoid crosses between related parents in fruit breeding programmes.
Subject(s)
Inbreeding , Prunus/genetics , Alleles , Crosses, Genetic , Fruit/genetics , Fruit/physiology , Genotype , Polymerase Chain Reaction , Prunus/physiology , Reproduction/physiology , Ribonucleases/genetics , Ribonucleases/metabolism , Trees/genetics , Trees/physiologyABSTRACT
During 2004, an unusual spread of Phytophthora infestans on tomato plants in greenhouses located in Almería and Granada provinces, southern Spain, was observed. Infected plants had water-soaked, brown spots on leaves and stems and necrotic areas with white mold on the surface of fruits. Three isolates were obtained by plating diseased tissue on V8 juice agar medium and maintained on rye agar at 18°C. These isolates were analyzed for the mating type. Crosses were carried out using V8 juice agar and rye agar. The two parental isolates US1 (A1) and US8 (A2) were both provided by W. E. Fry, Cornell University, Ithaca, NY. Two of the Spanish isolates were homothallic and the other isolate belonged to the uncommon mating type A1A2. To confirm the occurrence of the two mating types, 43 single-sporangium progeny were produced and analyzed from the A1A2 mating type. Thirty eight isolates were A1, two were A2, one was A1A2 mating type, and two were sterile. Assessment of five single-sporangium progeny from the homothallic type resulted in two A1, two homothallic, and one sterile isolate. A1A2 isolates produced oospores when crossed with either A1 or A2, but not when self-crossed. Previously, the A1A2 mating type has been found in Israel in the field and was obtained from oospores produced on tomato seeds (2,3). Since 2003, mating types of P. infestans isolates recovered from potato (60) and tomato (8) in southern Spain have been characterized. Seventy-five percent of the isolates recovered from potato were A1 and 25% were A2 mating types. Isolates recovered from tomato were 50% A1 and 50% A2 (1). To our knowledge, this is the first report of the occurrence of the A1A2 mating type and homothallic P. infestans isolates on tomato in Spain. References: (1) E. Andujar et al. Congr. Sociedad Española de Fitopatol. 12:244, 2004. (2) E. Rubin and Y. Cohen. Phytoparasitica 32:237, 2004. (3) E. Rubin and Y. Cohen. Plant Dis. 90:741, 2006.
ABSTRACT
INTRODUCTION: Plexiform neurofibroma in any location is one of the commonest complications associated with neurofibromatosis type 1 (NF1). Plexiform neurofibroma of the upper eyelid and orbit is usually associated with ipsilateral hemifacial hyperplasia. We present four patients with NF1 and plexiform neurofibroma of the eyelid and orbit associated with hemifacial hyperplasia, who also showed hyperplasia of the unilateral cerebral hemisphere. CASE REPORTS: There are four patients, three females and one male, who consulted because of NF1 with plexiform neurofibroma of upper eyelid and hemifacial hyperplasia. Upper eyelid involvement was observed since birth and progressed during the first years of life. The patients showed normal neurological and mental development without motor or cerebellar disorders. Magnetic resonance studies demonstrated the asymmetric hyperplasia of the ipsilateral hemisphere in all four cases and of the cerebellar hemisphere in one case. The degree of hemispheric hyperplasia was related to the size and extension of the plexiform neurofibroma, as well as to the severity of the hemifacial hyperplasia. In our case which had the plexiform neurofibroma extended to the neck and the upper thorax, the hyperplasia not only affected the cerebral hemisphere but also the ipsilateral cerebellar hemisphere. All parts of the hemisphere showed increased size. The cortex of the entire hemisphere showed normal differentiation of the subcortical white matter. CONCLUSION: NF1 appears to be related with facial and cerebral ipsilateral hemihyperplasia. The relation between the size and extension of the orbital, eyelid and facial plexiform neurofibroma and the degree of asymmetry of the hemispheric hyperplasia suggest that different influences of a still unknown agent, possibly a gene, obviously related to NF1, causes both the intracranial and extracranial abnormalities.
Subject(s)
Hyperplasia/etiology , Neurofibroma, Plexiform/etiology , Neurofibromatosis 1 , Adolescent , Adult , Brain Neoplasms/etiology , Brain Neoplasms/pathology , Child , Eyelid Neoplasms/etiology , Eyelid Neoplasms/pathology , Female , Humans , Hyperplasia/pathology , Male , Neurofibroma, Plexiform/pathology , Neurofibromatosis 1/complications , Neurofibromatosis 1/pathology , Orbital Neoplasms/etiology , Orbital Neoplasms/pathologyABSTRACT
Despite the importance of trafficking for regulating G protein-coupled receptor signaling, for many members of the seven transmembrane helix protein family, such as odorant receptors, little is known about this process in live cells. Here, the complete life cycle of the human odorant receptor OR17-40 was directly monitored in living cells by ensemble and single-molecule imaging, using a double-labeling strategy. While the overall, intracellular trafficking of the receptor was visualized continuously by using a GFP tag, selective imaging of cell surface receptors was achieved by pulse-labeling an acyl carrier protein tag. We found that OR17-40 efficiently translocated to the plasma membrane only at low expression, whereas at higher biosynthesis the receptor accumulated in intracellular compartments. Receptors in the plasma membrane showed high turnover resulting from constitutive internalization along the clathrin pathway, even in the absence of ligand. Single-molecule microscopy allowed monitoring of the early, dynamic processes in odorant receptor signaling. Although mobile receptors initially diffused either freely or within domains of various sizes, binding of an agonist or an antagonist increased partitioning of receptors into small domains of approximately 190 nm, which likely are precursors of clathrin-coated pits. The binding of a ligand, therefore, resulted in modulation of the continuous, constitutive internalization. After endocytosis, receptors were directed to early endosomes for recycling. This unique mechanism of continuous internalization and recycling of OR17-40 might be instrumental in allowing rapid recovery of odor perception.
Subject(s)
Receptors, Odorant/metabolism , Cell Membrane/metabolism , Cell Survival , Cells, Cultured , Clathrin/metabolism , Diffusion , Fluorescence , Humans , Ligands , Protein Structure, Tertiary , Protein Transport , Recombinant Fusion Proteins/metabolismABSTRACT
No disponible
Subject(s)
Humans , Codes of Ethics , Critical Care/ethics , Practice Patterns, Physicians'/ethics , Patient Rights/ethics , Personal Autonomy , Right to Die/ethics , Confidentiality/ethics , Quality of Health Care/ethics , Tissue Donors/ethics , Informed Consent/ethicsABSTRACT
We present a patient of 20 years of age with glutaric aciduria type 1 (GA1) and normal psychomotor development. Her symptoms consisted of a few convulsions between 2.5 and 4.5 years of age. She was diagnosed at 9 years of age because of the typical alterations of GA1 that appeared in computed tomography and magnetic resonance (MR) imaging studies. Enzymatic activity in fibroblasts culture was nonexistent and glutarate excretion was elevated in the annual controls where this was investigated from the diagnosis of the disease so far. MR studies showed hyposignal in T1 of the subcortical white matter, severe dilatation of the Sylvian region and temporal fossa subarachnoid spaces, and hypoplasia of the subjacent cerebral parenchyma and of both temporal lobes. The corpus callosum and the surrounding zones appeared very enlarged and with signal changes. Spectroscopic MR showed signs of membrane instability and cellular impoverishment in subcortical white matter and basal ganglia and presence of lactic acid. Macrocephaly always maintained centiles over 98. The patient has no abnormal movements or motor disturbances, her behavior and intelligence being normal and she is able to follow studies of middle level.
Subject(s)
Brain Diseases, Metabolic, Inborn/pathology , Brain/pathology , Glutarates/urine , Oxidoreductases Acting on CH-CH Group Donors/deficiency , Basal Ganglia/pathology , Brain Chemistry , Brain Diseases, Metabolic, Inborn/drug therapy , Brain Diseases, Metabolic, Inborn/enzymology , Brain Diseases, Metabolic, Inborn/genetics , Brain Diseases, Metabolic, Inborn/urine , Carnitine/therapeutic use , Cells, Cultured/enzymology , Child Development , Child, Preschool , Chromosomes, Human, Pair 19/genetics , Corpus Callosum/pathology , Female , Fibroblasts/enzymology , Follow-Up Studies , Glutaryl-CoA Dehydrogenase , Heterozygote , Humans , Intelligence , Lactic Acid/analysis , Magnetic Resonance Imaging , Mutation, Missense , Oxidoreductases Acting on CH-CH Group Donors/genetics , Riboflavin/therapeutic use , Seizures/etiology , Seizures/genetics , Sequence DeletionABSTRACT
Las lesiones traumáticas del páncreas son poco frecuentes pero se acompañan de una gran morbimortalidad, sobre todo si se demora el diagnóstico y consecuentemente el tratamiento, cosa relativamente habitual dada su escasa sintomatología. Por tanto, es muy importante valorar el mecanismo lesional que nos hará sospechar este tipo de lesión. La tomografía computarizada (TC) helicoidal es de gran utilidad diagnóstica. La actitud terapéutica está condicionada por la integridad o no del conducto pancreático. Presentamos el caso de un paciente con trauma abdominal cerrado en el que la TC de ingreso fue normal a pesar de tener una sección pancreática que se visualizó tres días después. Se complicó con una disfunción multiorgánica que evolucionó favorablemente
Traumatic lesions of the pancreas are not very common but accompanied by a high morbimortality rate, especially if diagnosis and subsequent treatment are delayed, which is relatively common given its poor symptomology. It is, therefore, very important to evaluate the lesional mechanism which would lead one to suspect this type of lesion. Spiral CAT is very useful diagnostic tool. Therapeutic approach is conditioned on pancreatic duct integrity. Herein is presented the case of a patient with closed abdominal trauma whose CT at admittance was normal in spite of having had a pancreatic lesion being observed three days later. It was further complicated by a multiorgan dysfunction which evolved favorably
Subject(s)
Humans , Abdominal Injuries , Pancreas/abnormalities , Pancreas/injuriesABSTRACT
We present a of 22 years old patient who has a severe cerebellar disease that started during the first years of life, borderline mental level, epilepsy and Klinefelter syndrome. Brain magnetic resonance (MR) imaging revealed swollen white matter with a loss of signal on T1-weighted slices and an increase in signal intensity on T2-weighted images in both cerebral hemispheres and in both cerebellar dentate nuclei. MRI alterations did not change during the studies performed from 4 to 21 years. Blood and urine were analyzed and showed great elevation of L-2-hydroxyglutaric acid (L-2-HGA) and more discrete elevation of its metabolites and lysine. The parents of the patient are first cousins.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Cerebellar Diseases , Glutarates/metabolism , Klinefelter Syndrome , Adolescent , Adult , Amino Acid Metabolism, Inborn Errors/metabolism , Amino Acid Metabolism, Inborn Errors/pathology , Cerebellar Diseases/metabolism , Cerebellar Diseases/pathology , Child , Child, Preschool , Female , Glutarates/chemistry , Humans , Lysine/metabolism , Magnetic Resonance Imaging , MaleABSTRACT
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder with a chronic progressive course. The gene, MLC1, has been localized on chromosome 22qtell and 26 different mutations have been described. We report two siblings of non-consanguineous parents who presented with characteristic features of MLC. They showed macrocephaly from the first months of life. After a short time, motor clumsiness, ataxia, seizures and psychomotor retardation were observed. During childhood, both patients had a coma that lasted several days following a minor head trauma. The eldest sister experienced a permanent deterioration of the clinical picture after the coma. Epilepsy and electroencephalographic alterations were chronic, tending to improve during adulthood. Cerebral biopsy showed normal or minor changes in the cortical grey matter, and in the white matter gliosis, increased extracellular spaces and decreased numbers of fibres with thin myelin sheets. We have followed the patients during 24 years, from the ages of 4 and 8 years to the their present ages of 28 and 32 years. Clinical and neuro-imaging follow-up showed a chronic course with more prominent progression of the white matter abnormalities than of the neurological features. A homozygous mutation of the MLC1 gene was found in both siblings. The eldest patient, 32 years-old, needs a wheel-chair but has a good contact with the family and surrounding people. The youngest, 28-years-old, shows mild ataxia, spasticity and motor clumsiness, but she is able to participate in activities of daily life.
Subject(s)
Brain Diseases , Brain Diseases/complications , Brain Diseases/diagnosis , Brain Diseases/genetics , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Membrane Proteins/genetics , Mutation , Time FactorsABSTRACT
INTRODUCTION: Non-ketotic hyperglycinemia is a congenital error in the breakdown of glycine. The most common type is the classical neonatal form, which begins at the age of a few days with symptoms of lethargy, hypotonia, myoclonia, convulsions, apneas and, frequently, ends in death. Survivors usually develop intractable epilepsy and mental retardation. There is no effective treatment for this condition, but trials have been carried out with a therapy that diminishes the levels of glycine, benzoate (BZ), and another that blocks the excitatory effect in N-methyl-D-aspartate receptors: dextromethorphan (DTM). CASE REPORT: We report on the progress of a classical neonatal case, which began at the age of a few hours with hypotonia and stupor, without myoclonias or seizures, but with a suppression wave trace on the electroencephalogram (EEG). Cerebrospinal fluid (CSF) showed glycine levels of 141 micromol/L (the normal level is 6.66 +/- 2.66 micromol/L), with a CSF/plasma ratio of 0.19 (the normal ratio is < 0.02). Treatment was started on the thirteenth day with BZ and DTM, and alertness and eye fixation improved in just three days; at the same time the EEG readings become normal. The glycine level in plasma returned to normal at two months and that in CSF was considerably reduced, although with CSF/plasma levels that were still high. At present the patient is 4 years old, has never had convulsions, EEG results have always been normal, and continues with BZ, DTM, carnitine and diet. The patient has presented a high degree of hypermotoric behaviour, but is currently more attentive and more sociable, has been walking from the age of 35 months and has a quotient in the different areas of development of 40-50. CONCLUSIONS: The clinical progress made by our patient could be said to be anything but negligible, and we therefore recommend that treatment should be started as early as possible after diagnosis.