ABSTRACT
Glycogen Storage Disease (GSD) IXd, caused by PHKA1 gene mutations, is an X-linked rare disorder that can be asymptomatic or associated with exercise intolerance. GSD type II is an autosomal recessive disorder caused by mutations in the GAA gene that lead to severe cardiac and skeletal muscle myopathy. We report the first case of co-occurrence of type IXd and type II GSDs in a 53-year-old man with an atypical glycogen storage disease presentation consisting in myalgia in the lower limbs at both rest and after exercise and increased levels of transaminases from the age of 16. At the age of 43, the patient presented a steppage gait, inability to run and walk on his heels, hypotrophy of the pectoral and proximal muscles, reflexes not elicitable, and CK levels 3.6 times the upper reference limit. Next Generation Sequencing (NGS) identified one variant in the PHKA1 gene, c.1360A > G p.Ile454Val (exon 14) inherited by his mother, and two heterozygous variants in the GAA gene, c.784G > A (exon 4) and c.956-6T > C (exon 6). A review of GSD IXd cases reported to date in the literature is also provided.
Subject(s)
Genetic Diseases, X-Linked , Glycogen Storage Disease Type II , Glycogen Storage Disease , Male , Humans , Middle Aged , Glycogen Storage Disease/complications , Glycogen Storage Disease/diagnosis , Glycogen Storage Disease/genetics , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/genetics , PhenotypeABSTRACT
The aim of this longitudinal cohort study, is to provide more insight into the pattern of brain abnormalities, and possible consequences for cognitive functioning, in patients with classic infantile Pompe disease. We included 19 classic infantile Pompe patients (median age last assessment 8.9 years, range 1.5-22.5 years; 5/19 CRIM negative), treated with ERT. Using MR imaging of the brain (T1, T2, and FLAIR acquisitions), we classified progression of brain abnormalities on a 12-point rating scale at multiple time points throughout follow-up. Additionally we noted specific white matter patterns and examined atrophy. Cognitive development was studied using Wechsler IQ assessments obtained by certified neuropsychologists. The association between age and cognitive functioning, and MRI ratings and cognitive functioning was assessed by linear regression models. All but one patient developed brain abnormalities. The abnormalities progressed in a similar pattern throughout the brain, with early involvement of periventricular white matter, later followed by subcortical white matter, gray matter structures, and juxtacortical U-fibers. We found a significant decline (p < 0.01), with increasing age for full scale IQ, performance IQ and processing speed, but not for verbal IQ (p = 0.17). Each point increment in the 12-point MRI rating scale was associated with a significant decline (3.1-6.0 points) in all the IQ index scores (p < 0.05). The majority of long-term surviving patients in our cohort develop incremental brain MRI abnormalities and decline in cognitive functioning. This highlights the need for new therapies that can cross the blood-brain barrier in order to treat this CNS phenotype.
Subject(s)
Brain , Cognition , Glycogen Storage Disease Type II , Magnetic Resonance Imaging , Humans , Male , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/pathology , Female , Infant , Brain/pathology , Brain/diagnostic imaging , Child, Preschool , Adolescent , Child , Longitudinal Studies , Young Adult , Disease Progression , White Matter/pathology , White Matter/diagnostic imaging , Enzyme Replacement Therapy , AdultABSTRACT
BACKGROUND: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. MATERIAL AND METHODS: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. RESULTS: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. CONCLUSIONS: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.
Subject(s)
Diaphragm , Electromyography , Glycogen Storage Disease Type II , Motor Neurons , Muscle Weakness , Phrenic Nerve , Humans , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/physiopathology , Male , Diaphragm/physiopathology , Female , Middle Aged , Muscle Weakness/etiology , Muscle Weakness/physiopathology , Phrenic Nerve/physiopathology , Motor Neurons/physiology , Motor Neurons/pathology , Adult , Neural Conduction/physiology , Muscle Fibers, Skeletal/pathology , Muscle Fibers, Skeletal/physiology , Aged , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Prospective Studies , Action Potentials/physiologyABSTRACT
INTRODUCTION: Late-onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α-glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long-term treatment results vary. Avalglucosidase alfa demonstrated non-inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa. METHODS: Data from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow-up. Respiratory (forced vital capacity [FVC]) and motor functions (Six-Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values. RESULTS: Twenty-nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: -1 m/year on the 6MWT after the switch versus -63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different. DISCUSSION: At the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening. CONCLUSION: Switching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization.
Subject(s)
Enzyme Replacement Therapy , Glycogen Storage Disease Type II , alpha-Glucosidases , Humans , Glycogen Storage Disease Type II/drug therapy , Glycogen Storage Disease Type II/complications , Male , Middle Aged , Female , France , alpha-Glucosidases/therapeutic use , Enzyme Replacement Therapy/methods , Aged , Adult , Cohort Studies , Treatment Outcome , Registries , Disease Progression , Walk Test , Drug SubstitutionABSTRACT
INTRODUCTION: The standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. METHOD: We identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. RESULTS: All six IOPD patients (4 males/2 females) had been treated with ERT for 12-15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9-15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. DISCUSSION: Among a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.
Subject(s)
Glycogen Storage Disease Type II , Child , Male , Female , Humans , Adolescent , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnostic imaging , Glycogen Storage Disease Type II/drug therapy , Brain/diagnostic imaging , Magnetic Resonance Imaging , Seizures/diagnostic imaging , Seizures/etiology , Risk Factors , Enzyme Replacement Therapy/methods , alpha-Glucosidases/therapeutic useABSTRACT
Abstract Introduction: Anti-nucleosome and anti-C1q antibodies demonstrated an association with the development of glomerulonephritis in systemic lupus erythematosus (SLE). Some investigators have proposed that monitoring anti- C1q and anti-nucleosome antibodies might be valuable for making predictions about lupus nephritis (LN) and assessment of disease activity as a non-invasive biological marker of renal disease. Objectives: The current study was proposed to investigate the presence of anti-C1q and anti-nucleosome antibodies in the sera of Egyptian patients with SLE and their association with LN. Methods: Eighty patients with SLE were included. Patients were classified into, a LN group including 40 cases with active LN (based on the results of renal biopsy and renal SLEDAI≥4) and a non renal SLE group including 40 patients (with no clinical or laboratory evidence of renal involvement that were attributed in the past or present to SLE). They were subjected to full medical history taking, clinical examination, routine laboratory investigations, measurement of antinuclear antibody (ANA), anti-ds DNA, anti-C1q & anti-nucleosome antibodies. Results: Anti-C1q antibody showed a statistically significant association with the presence of vasculitis and nephritis while anti-nucleosome antibody didn't show a significant association with the presence of any clinical features. Double positivity of anti-nucleosome and anti-C1q antibodies showed a statistically significant association with the presence of vasculitis and photosensitivity, high ECLAM score, elevated ESR, low serum albumin and low C3 levels. Conclusion: Serum anti-C1q antibody has a significant association with LN while double positive antibodies have a significant association with vasculitis and low C3 levels in Egyptian patients with SLE.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Pulmonary Medicine/methods , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Dried Blood Spot Testing/standards , Late Onset Disorders/diagnosis , Lung Diseases/complications , Biopsy , Glycogen Storage Disease Type II/blood , Glycogen Storage Disease Type II/enzymology , Early Diagnosis , alpha-Glucosidases/metabolism , Late Onset Disorders/blood , Late Onset Disorders/enzymology , Italy , Lung Diseases/blood , Muscles/surgery , Muscles/enzymologyABSTRACT
La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.
Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.
Subject(s)
Humans , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/therapy , Argentina , Glycogen Storage Disease Type II/complications , Age of Onset , Expert TestimonyABSTRACT
La artrogriposis es un síndrome complejo, que responde etiológicamente a numerosas causas congénitas y adquiridas. Presentamos un caso familiar de artrogriposis. La necropsia aportó el hallazgo de inclusiones rojo-púrpura en el sarcoplasma del tejido muscular, sugestiva de miopatía por nemalinas
Arthrogryposis is a complex syndrome, the aetiology of which can be traced to numerous congenital and acquired causes. We present a case of familiar arthrogryposis. Necropsy revealed red-purple rod-like structures in the sarcoplasm of the muscle tissue, suggestive of nemaline myopathy
Subject(s)
Humans , Female , Pregnancy , Adult , Myopathies, Nemaline/complications , Myopathies, Nemaline/diagnostic imaging , Arthrogryposis/etiology , Arthrogryposis/genetics , Amniocentesis/methods , Muscular Atrophy, Spinal/diagnostic imaging , Muscles/diagnostic imaging , Muscles/pathology , Muscular Atrophy, Spinal/complications , Gaucher Disease/complications , Glycogen Storage Disease Type II/complications , Mucopolysaccharidosis VII/complications , Mucopolysaccharidosis VII/diagnostic imagingABSTRACT
Introducción. La enfermedad de Pompe es un trastorno generalizado progresivo producido por el déficit de la enzima alfaglucosidasa ácida (AGA) de los lisosomas. Se presentan tres casos manifestados de forma muy diferente y tratados con terapia enzimática sustitutiva (TES), con evolución favorable. Casos clínicos. Caso 1: varón de 3 meses, con debilidad y rechazo de la alimentación, hepatomegalia leve, ligera macroglosia e hipotonía, y aumento de las enzimas musculares. Caso 2: varón de 5 meses, con retraso del desarrollo motor, sordera neurosensorial grave, trastornos respiratorios de repetición de evolución tórpida, hipotonía y leve elevación de la creatincinasa. Caso 3: varón de 22 años con disnea progresiva, con antecedentes de elevación de la creatincinasa y las transaminasas, e hipercolesterolemia. Sufrió insuficiencia respiratoria grave que precisó intubación endotraqueal. La biopsia muscular presentó depósitos de glucógeno sugestivos de la enfermedad. En los tres casos, el estudio electromiográfico dio un patrón característico, con descargas pseudomiotónicas, y se confirmó el déficit de AGA en los linfocitos. Se encontró una mutación en un caso y dos mutaciones en los otros dos. Todos recibieron TES con evolución favorable: desaparición de las alteraciones cardíacas en el caso 1, mejoría en los hitos motores en los dos casos infantiles y retirada del respirador en el caso 3. Conclusión. La enfermedad de Pompe tiene una amplia variabilidad en la expresión clínica. La TES consigue una buena respuesta, especialmente en las formas infantiles. La supervivencia a largo plazo de las formas infantiles tratadas permitirá conocer más aspectos del curso de la enfermedad (AU)
Introduction. Pompe disease is a generalized progressive disease caused by a deficiency of the lysosome enzyme acid alphaglucosidase (GAA). We present three cases with different clinical symptomatology and treated with enzyme replacement therapy (ERT) with positive evolution. Case reports. Case 1: three-month old male, with weakness and rejecting meals; mild hepatomegaly, discrete macroglossia and muscular hypotony; and increased muscular enzymes. Case 2: five-month old male, with delayed motor development, severe neurosensory deafness, and respiratory disorder of difficult evolution; muscular hypotony; and mild increase in creatine kinase. Case 3: 22-year old male, with progressive dyspnea, with history of increased creatine kinase and transaminases, and hypercholesterolemia. He suffered from severe respiratory failure requiring endotraqueal intubation Muscular biopsy showed glycogen storage suggestive of Pompe disease. In the three cases, the EMG showed a characteristic pattern with pseudomyotonic discharges and the deficiency in GAA was confirmed in lymphocytes. One single mutation was observed in one case and two in the other two cases. Every patient received ERT showing a favorable evolution; with disappearance of cardiac disorders in case 1, improvement in motor development in both infants and no longer need for mechanical ventilation in case 3. Conclusion. Pompe disease has a wide variability in clinical expression. ERT achieves a good response, especially in infant forms of the disease. The survival of treated patients with these Pompe disease forms will allow knowing further the course of the disease (AU)
Subject(s)
Adolescent , Child , Humans , Male , Glycogen Storage Disease Type II/genetics , Glycogen Storage Disease Type II/metabolism , Enzyme Therapy/methods , Enzyme Therapy/standards , Muscle, Skeletal/abnormalities , Hepatomegaly/pathology , Deafness/diagnosis , Dyspnea/genetics , Quality of Life/psychology , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/pathology , Enzyme Therapy/classification , Enzyme Therapy , Muscle, Skeletal/injuries , Hepatomegaly/metabolism , Deafness/complications , Dyspnea/metabolismABSTRACT
La enfermedad de Pompe (glucogenosis tipo II) es una enfermedad de depósito lisosomal, autosómica recesiva causada por una deficiencia de ácido alfa-glucosidasa. Los tumores neuroendocrinos tímicos son neoplasias primarias con diferenciación neuroendocrina que generalmente se presentan como una masa en el mediastino anterior. Ambas enfermedades se consideran raras en sí mismas. En nuestro conocimiento, la enfermedad de Pompe y un tumor neuroendocrino del timo en el mismo paciente no ha sido antes comunicada. No pudimos encontrar la plausibilidad biológica entre ambas enfermedades. Se necesitan más estudios para confirmar el hallazgo y para aumentar aún más nuestra comprensión de esta asociación. Los datos clínicos de los estudios epidemiológicos, los informes de casos, las series de casos y los pequeños ensayos clínicos abiertos o controlados pueden definir tanto la plausibilidad clínica como la causalidad entre las dos enfermedades.
Pompe disease (glycogenosis type II) is an inherited autosomal recessive lysosomal storage disease caused by a deficiency of acid alpha-glucosidase. Thymic neuroendocrine tumors, are primary thymic neoplasms with neuroendocrine differentiation that generally present as a mass within the anterior mediastinum. Both diseases are considered rare. To our knowledge the co-existence of Pompe disease and thymic neuroendocrine tumor in the same patient has not been previously reported. We could not find biological plausibility between both diseases. Further studies are needed to confirm the finding and to further increase our understanding of this association. Clinical data from epidemiological studies, case reports, case series and small formal open or controlled clinical trials may define both clinical plausibility and causality between the two conditions.
Subject(s)
Humans , Male , Adult , Middle Aged , Thymus Neoplasms/complications , Glycogen Storage Disease Type II/complications , Carcinoma, Neuroendocrine/complications , Thymus Neoplasms/diagnosis , Glycogen Storage Disease Type II/diagnosis , Tomography Scanners, X-Ray Computed , Carcinoma, Neuroendocrine/diagnosis , Rare Diseases/diagnosisABSTRACT
No disponible
Subject(s)
Humans , Male , Infant, Newborn , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/enzymology , Glycogen Storage Disease Type II/therapy , Cardiomegaly/complications , Cardiomegaly , Sensitivity and Specificity , Predictive Value of Tests , Glycogen Storage Disease Type II , Radiography, Thoracic , ElectrocardiographyABSTRACT
Las llamadas enfermedades congénitas del metabolismo(ECM) son consecuencia de alteraciones bioquímicasde origen génico que tienen como consecuencia la alteraciónde una proteína. Dependiendo de la función de estaproteína, ya sea como un enzima; como una hormona; comoun receptor-transportador de membrana celular; o formandoparte de una organela celular (lisosoma, peroxisoma)surgen diferentes grupos de enfermedades, lo cual originala característica más destacada de los errores innatos delmetabolismo (EIM) que es su gran heterogeneidad clínica.La mayoría de estas enfermedades son autosómico-recesivas,con un número limitado de portadores asintomáticos,pero también las hay regidas por una herencia de carácterautonómica dominante o ligada al cromosoma X. Uno a uno,realmente los ECM son muy poco frecuentes pero en suconjunto los ECM (de los cuales hay descritos en el momentoactual más de 500) pueden afectar al 1/500 recién nacidos.Una característica común a muchos ECM es la posibilidadde tratamiento dietético y el tratamiento con sustituciónenzimática.Desde el punto de vista práctico es útil considerar suclasificacion atendiendo al momento de inicio de los síntomasy a la forma de presentación de las manifestaciones clínicas.Desde esta perspectiva y con fines fundamentalmentedidácticos se deben considerar los siguientes grupos:ECM del metabolismo intermediario, (tipo intoxicación, ytipo déficit energético). Errores congénitos del metabolismode las organelas celulares, y EMCM complejos por alteraciónde ciclos y otros. Se presentan de forma resumidalos aspectos clínicos, diagnósticos y terapéuticos de unaenfermedad de cada tipo de las descritas anteriormente:hiperfenilalaninemias, deficiencias de la fosforilación oxidativamitocondrial (OXPHOS) y enfermedades lisosomales
So-called congenital metabolic diseases (CMD) are aconsequence of biochemical alterations originating in thegenes that result in the alteration of a protein. Dependingon this proteins function - whether as an enzyme, a hormone,a receiver-transporter of a cellular membrane orforming part of a cellular organelle (lysosome, peroxysome) different groups of diseases emerge, which cause the mostoutstanding characteristic of inborn errors of metabolism(IEM): their clinical heterogeneity. The majority of these diseasesare autosomal recessive, with a limited number ofasymptomatic carriers, but there are also those ruled by anautonomous, dominant character inheritance or linked tothe X chromosome. Taken individually, CMDs are highlyinfrequent, but taken as a whole CMDs (of which over 500have been described to date) can affect 1/500 of the newborn.A common characteristic of many CMDs is the possibilityof dietary treatment and treatment with enzymaticreplacement.For essentially didactic purposes the following groupsshould be considered: CMDs of the intermediary metabolism(whose types are intoxication and energy deficit),CMDs of cellular organelles, complex CMDs due to cyclealterations and others. A summary is presented of the clinical,diagnostic and therapeutic aspects of one disease ofeach type of those previously described: hyperphenylalaninemias,deficiencies of the mitochondrial oxidative phosphorilation(OXPHOS) and lysosomal storage diseases
Subject(s)
Humans , Male , Female , Steroid Metabolism, Inborn Errors/complications , Steroid Metabolism, Inborn Errors/diagnosis , Rare Diseases/congenital , Rare Diseases/metabolism , Oxidative Phosphorylation , Oxidative Phosphorylation Coupling Factors/deficiency , Phenylketonurias/complications , Phenylalanine/therapeutic use , Carnitine/therapeutic use , Dichloroacetic Acid/therapeutic use , Glycogen Storage Disease Type II/complications , Steroid Metabolism, Inborn Errors/classification , Sensitivity and Specificity , Sodium Bicarbonate/therapeutic use , Thyroxine/therapeutic use , Lipidoses/complicationsABSTRACT
Las miopatías metabólicas son trastornos de la producción de energía muscular que provocan una disfunción muscular esquelética. Las miopatías relacionadas con el ejercicio comprenden un grupo de enfermedades musculares (Tabla 1y 2) con sintomatología inducida por el ejercicio muscular o situaciones de demanda energética. Las enfermedades del metabolismo energético muscular son un grupo de enfermedades heterogéneas desde el punto de vista genético, clínico y bioquímico. Esquemáticamente desde el punto de vista bioquímico pueden ser agrupadas en tres categorías, así las podemos subdividir en alteraciones del metabolismo de los hidratos de carbono, trastornos del metabolismo lipídico y alteraciones de la función mitocondrial. La genética es el área donde en los últimos años las aportaciones han sido más relevantes y numerosas, gracias a los avances proporcionados por las técnicas de genética molecular. El conocimiento, localización y clonaje de los distintos genes han facilitado enormemente el avance científico de estas enfermedades (AU)
Metabolic myopathies are disorders of muscle energy production that impair skeletal muscle function. Exercise-related myopathies are a group of muscle diseases in which symptoms a retriggered during muscle exercise or in situation of increased metabolic demands. This group of diseases is heterogeneous from a genetic, clinical and biochemical point of view. From a biochemical perspective, they can be grouped into three categories: alterations in carbohydrate and lipid metabolism, respectively, and alterations in mitochondrial function. The main advances in the understanding of these diseases come mainly from molecular biology techniques (AU)
Subject(s)
Humans , Male , Female , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Muscular Diseases/metabolism , Exercise/physiology , Energy Metabolism/genetics , Energy Metabolism/physiology , Lipid Metabolism Disorders/genetics , Lipid Metabolism Disorders/pathology , Mitochondria, Muscle/genetics , Mitochondria, Muscle/metabolism , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Carnitine/deficiency , Carnitine/metabolismABSTRACT
La glucogenosis secundaria o síndrome de Mauriac es la primera causa de hepatomegalia y alteración de las pruebas de función hepática en adolescentes y adultos diabéticos. Es relativamente frecuente en mujeres jóvenes con diabetes tipo 1 y puede cursar semejando un abdomen agudo con dolor en el hipocondrio derecho, náuseas y vómitos. Estos pacientes deben ser manejados mediante una actitud expectante, ya que con el buen control glucémico y el ajuste de las dosis de insulina, el cuadro se suele autolimitar en una semana (AU)
Subject(s)
Adolescent , Female , Humans , Glycogen Storage Disease Type II/complications , Hepatomegaly/etiology , Abdomen, Acute/diagnosis , Abdomen, Acute/surgery , Diabetes Mellitus, Type 1/complications , Diagnosis, Differential , Glycogen Storage Disease/diagnosisABSTRACT
Objetivo: A Glicogenose tipo II ou Doença de Pompe é uma doença de armazenamento do glicogênio causada por deficiência enzimática. Pode manifestar-se em lactantes com hipotonia, cardiomegalia e hepatomegalia. As enzimas musculares estão elevadas, o ECG mostra intervalo PR curto, a radiografia de tórax apresenta cardiomegalia importante e a ecocardiografia mostra hipertrofia miocárdica. Firma-se diagnóstico através de análise histopatológica em biópsia de músculo estriado. Material e método: Os autores descrevem um caso de Glicogenose tipo II(Doença de Pompe) que cursou com insuficiência respiratória secundária a insuficiência cardíaca severa e discutem o diagnóstico, a terapêutica e a orientação a família utilizadas nesta doença potencialmente fatal. Conclusões: A Glicogenose tipo II, apesar de rara, dever ser considerada no diagnóstico diferencial nos quadros de insuficiência cardíaca relacionados a miocardiopatia, nos primeiros meses de vida
Subject(s)
Humans , Infant , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/therapy , Respiratory Insufficiency , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/therapyABSTRACT
La enfermedad de Pompe es una de las glicogenosis o enferemdad de depósito del glucógeno, que se transmite con carácter autosómico recesivo y es producida por la deficiencia de la enzima maltasa ácida que degrada glicógeno en los lisosomas. Se dintinguen tres tipos de enferemdad de Pompe : el tipo infantil que se acracteriza por la acumulación de glicógeno en el hígado, músculo esquelético y cardíaco y células del sistema nervioso central; los pacientes fallecen usaulamente antes de los dos años por falla cardiorespiratoria; el fenotipo juvenil se presenta en niños o jóvenes, no siempre involucra el sistema nervioso central o el músculo cardíaco y los pacientes fallecen generalmente durante la segunda década de vida; el tipo adulto cursa con distrofia muscular, algunas veces asociada con deficiencia respiratoria por compromiso de los músculos diagragma e intercostales. El pronóstico depende del grado de la falla respiratoria, la cual es causa principal de la muerte de estos pacientes. En este trabajo se informa el caso de un niño de seis meses de edad, afectado por cardiomegalia, retardo psicomotor e hipotonía. La confirmación bioquímica de la enfermedad se hizo determinando la actividad de la alfa-glucosidasa en leucocitos por dos métodos diferentes, usando como sustrato maltasa o el sustrato fluorescente 4-metil-umbeliferil-glucósido. La actividad de la maltasa ácida en leucocitos, usando maltosa como sustrato fue de 6,36Umol glucosa/min/g, con un valor de referencia entre 16-63 Umoles/glucosa/min/g de proteína. Con el sustrato fluorogénico, la activida en el paciente fue de 34.48 nanomoles/h/mg, de proteína, para un valor de referencia entre 194 y 258. La actividad en leucocitos tanto del padre como de la madre corresponde a un 60 por ciento del valor normal, hallado en personas en cuya familia no se sospecha dicha enfermedad.
Subject(s)
Humans , Male , Infant , Glycogen Storage Disease Type II/surgery , Glycogen Storage Disease Type II/classification , Glycogen Storage Disease Type II/complications , Glycogen Storage Disease Type II/diagnosis , Glycogen Storage Disease Type II/diet therapy , Glycogen Storage Disease Type II/epidemiology , Glycogen Storage Disease Type II/etiology , Glycogen Storage Disease Type II/physiopathology , Glycogen Storage Disease Type II/mortality , Glycogen Storage Disease Type II/pathology , Glycogen Storage Disease Type II/drug therapy , Glycogen Storage Disease Type II , Glycogen Storage Disease Type II/therapyABSTRACT
We describe a case of the juvenile form of Pompe's disease that presented as primary alveolar hypoventilation due to respiratory muscle involvement. This 17-year-old girl had been asymptomatic until this admission, although she had a delayed puberty. Arterial blood gas analysis, pulmonary function test as well as physical findings were compatible with chronic alveolar hypoventilation syndrome. Since she had lower extremity muscle weakness and pseudomyotonic discharge on electromyography a muscle biopsy was done, which revealed glycogen storage disease. The patient was managed successfully with nasal intermittent positive pressure ventilation.