RESUMO
Background: Pompe disease (PD) is a rare autosomal recessive genetic disorder (1 in 14,000) which affects the synthesis of acid alpha-glucosidase (AGA), leading to intralysosomal glycogen accumulation in muscle tissue. The clinical presentation is heterogeneous, with variable degrees of involvement and progression, classifiable based on the age of onset into infantile (classic or non-classic) and late-onset forms (juvenile or adult). The diagnostic test of choice is the enzymatic analysis of AGA, and the only pharmacological treatment is enzyme replacement therapy (ERT). This document aims to report a clinical case of late-onset PD. Clinical case: 14-year-old male who started at the age of 5 with postural alterations, gait changes, and decreased physical performance compared to his peers. A diagnostic evaluation was initiated in 2022 due to worsening neuromuscular symptoms, accompanied by dyspnea, tachycardia, and chest pain. A suspicion of a lysosomal storage myopathy was established, and through enzymatic determination of AGA the diagnosis of PD was confirmed. The study of the GAA gene revealed the association of 2 previously unreported genomic variants. ERT was initiated, resulting in clinical improvement. Conclusions: The age of symptom onset, severity of clinical presentation, and prognosis of the disease depend on the specific mutations involved. In this case, the identified genetic alterations are associated with different phenotypes. However, based on the clinical presentation, it is categorized as juvenile PD with an indeterminate prognosis.
Introducción: la enfermedad de Pompe (EP) es un padecimiento genético autosómico recesivo poco frecuente (1:14,000) que afecta la síntesis de alfa-glucosidasa ácida (AGA) y condiciona un depósito de glucógeno intralisosomal en tejido muscular. La presentación clínica es heterogénea, con grados variables de afectación y progresión, clasificable según la edad de aparición en infantil (clásica y no clásica) y de inicio tardío (juvenil o de adultez). La prueba diagnóstica de elección es el análisis enzimático de AGA y el único tratamiento farmacológico es la terapia de reemplazo enzimático (TRE). Este documento tiene como objetivo reportar un caso clínico de EP de inicio tardío. Caso clínico: paciente de sexo masculino de 14 años que comenzó a los 5 años con alteraciones de la postura, marcha y desempeño físico. Se inició protocolo de estudio ante agravamiento de los síntomas neuromusculares, a los que se agregaron disnea, taquicardia y dolor torácico. Se sospechó de una miopatía metabólica de depósito lisosomal y mediante determinación enzimática de AGA se confirmó el diagnóstico de EP. El estudio molecular del gen GAA reportó una asociación de 2 variantes genómicas no descritas previamente. Se empleó la TRE con mejoría clínica. Conclusiones: la edad de inicio del cuadro clínico, severidad y pronóstico dependen de las mutaciones presentadas. En este caso, las alteraciones genéticas encontradas están relacionadas con diferentes fenotipos; no obstante, por clínica es categorizado como una EP juvenil con pronóstico indeterminado.
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Genótipo , Doença de Depósito de Glicogênio Tipo II , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , Masculino , Adolescente , alfa-Glucosidases/genética , México , Terapia de Reposição de EnzimasRESUMO
Late-onset Pompe disease manifests predominantly in the proximal lower limbs and may be mistaken for an inflammatory myopathy. A 46-year-old man with acromegaly had an 8-year history of progressive weakness. His myopathy was initially attributed to the acromegaly, but severe progression prompted a muscle biopsy, which suggested an inflammatory myopathy. However, his weakness progressed despite treatment for polymyositis. His muscle ultrasound scan pattern was more suggestive of Pompe disease than polymyositis, and Pompe disease was confirmed by genetic and enzymatic testing. Patients with apparent polymyositis, which persists despite treatment, require reconsideration of the diagnosis, with particular attention to treatable genetic causes.
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Acromegalia , Doença de Depósito de Glicogênio Tipo II , Miosite , Polimiosite , Masculino , Humanos , Pessoa de Meia-Idade , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Polimiosite/diagnóstico , Polimiosite/patologia , Erros de DiagnósticoRESUMO
Pompe disease (PD) is an inborn error of metabolism caused by α-glucosidase acid enzyme deficiency. It significantly impacts patients' health and life quality and may lead to death in the first few years of life. Among the well-established diagnostic methods, urinary glucose tetrasaccharide (Glc4) screening by high performance-liquid chromatography has been helpful in monitoring Glc4 levels in patients on enzyme replacement therapy, demonstrating therapy efficacy. However, the specimen shipping process from a sample collecting location to a specialized laboratory for monitoring the Glc4 is costly and presents preanalytical challenges. In this work, we developed a filter paper based-urine collection kit to facilitate specimen shipment, and liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) analysis to determine Glc4 and creatinine in dried urine on filter paper. The LC-HRMS was based on a combination of targeted and untargeted screening on the same specimen injection and was successfully developed and validated. Bland-Altman statistics revealed a good relationship between dried and liquid urine samples and Glc4 and creatinine. Glc4 and other metabolites in dried urine showed stability for at least 7 days at 4 and 22 °C, and 3 days at 50 °C. The stability of the analytes and the efficiency of the kit were tested simulating real conditions by sending it by post. After two days in transit without refrigeration, the stability of compounds was maintained, showing the reliability of the urine collection kit and analysis method to determine the PD biomarker Glc4.
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Doença de Depósito de Glicogênio Tipo II , Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/urina , Creatinina , Coleta de Urina , Reprodutibilidade dos Testes , Espectrometria de Massas , Cromatografia Líquida/métodosRESUMO
INTRODUCTION: Pompe disease is a rare, lysosomal disorder, characterized by intra-lysosomal glycogen accumulation due to an impaired function of α-glucosidase enzyme. The laboratory testing for Pompe is usually performed by enzyme activity, genetic test, or urine glucose tetrasaccharide (Glc4) screening by HPLC. Despite being a good preliminary marker, the Glc4 is not specific for Pompe. OBJECTIVE: The purpose of the present study was to develop a simple methodology using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for targeted quantitative analysis of Glc4 combined with untargeted metabolic profiling in a single analytical run to search for complementary biomarkers in Pompe disease. METHODS: We collected 21 urine specimens from 13 Pompe disease patients and compared their metabolic signatures with 21 control specimens. RESULTS: Multivariate statistical analyses on the untargeted profiling data revealed Glc4, creatine, sorbitol/mannitol, L-phenylalanine, N-acetyl-4-aminobutanal, N-acetyl-L-aspartic acid, and 2-aminobenzoic acid as significantly altered in Pompe disease. This panel of metabolites increased sample class prediction (Pompe disease versus control) compared with a single biomarker. CONCLUSION: This study has demonstrated the potential of combined acquisition methods in LC-HRMS for Pompe disease investigation, allowing for routine determination of an established biomarker and discovery of complementary candidate biomarkers that may increase diagnostic accuracy, or improve the risk stratification of patients with disparate clinical phenotypes.
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Doença de Depósito de Glicogênio Tipo II , Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/urina , Metabolômica/métodos , Biomarcadores/urina , Fenótipo , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. OBJECTIVE: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. METHODS: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. RESULTS: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. CONCLUSION: There was a good correlation between genotype and phenotype in children with Pompe disease.
INTRODUCCIÓN: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. OBJETIVO: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. MÉTODOS: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. RESULTADOS: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. CONCLUSIÓN: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.
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Doença de Depósito de Glicogênio Tipo II , Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Genótipo , Mutação , Fenótipo , Terapia de Reposição de EnzimasRESUMO
INTRODUCTION: Pompe disease (PD) is a rare metabolic myopathy with an ample and heterogeneous clinical spectrum, particularly late onset PD (LOPD), which is characterized by appearance at older age and slower disease progression, leading to diagnostic confirmation difficulty and delay. AIM: To describe the genotype and clinical characteristics of Mexican patients with LOPD. MATERIAL AND METHODS: Clinical information from 19 Mexican patients with LOPD confirmed with enzyme activity and GAA gene analysis was reviewed. Genetic information of our population was crossed with international genetic databases. RESULTS: Median age between onset of symptoms and diagnosis was 19 years (range 2-43) and diagnostic confirmation 36 years (range 9-52). Most frequently referred symptoms were proximal axial weakness (n = 17; 89.5%), waddling gait (n = 17; 89.5%) and hyperlordosis (n = 7; 36.8%). Sixteen patients (84.2%) were evaluated with electromyography; a myopathic pattern was reported in 11 (57.8%), but only in 5 patients (26%) paraspinal muscle evaluation was included. The most pathogenic mutations in our group were c.-32-13T>G, c.1799G>A and c.1082C>T. CONCLUSIONS: Similar to other international publications, LOPD in Mexico is clinically heterogeneous; patients may delay years before diagnosis is established. Axial and proximal weakness is the most frequent clinical feature; thus, electromyography with paraspinal muscle evaluation is essential. Except for one, the mutations found in our patients have been previously reported in PD genetic databases.
TITLE: Enfermedad de Pompe de inicio tardío: análisis de una casuística de 19 pacientes mexicanos.Introducción. La enfermedad de Pompe es una miopatía metabólica rara con espectro clínico heterogéneo, especialmente la de inicio tardío, cuya sintomatología es de progresión más lenta y representa un gran reto diagnóstico. Objetivo. Describir el genotipo y las características clínicas de pacientes mexicanos con Pompe de inicio tardío (LOPD). Material y métodos. Se incluyó a 19 pacientes mexicanos con LOPD confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se evaluaron datos clínicos y se revisaron las mutaciones en bases de datos genómicas. Resultados. La mediana de edad de inicio de los síntomas fue de 19 años (rango: 2-43 años), y la edad de diagnóstico, de 36 años (rango: 9-52 años). Los síntomas más frecuentes fueron debilidad axial y proximal (n = 17; 89,5%), marcha basculante (n = 17; 89,5%) e hiperlordosis (n = 7; 36,8%). A 16 pacientes (84,2%) se les realizó electromiografía; 11 (57,8%) describieron patrón miopático y sólo en cinco pacientes (26%) se incluyó la valoración de los músculos paraespinales. Las variantes patogénicas más frecuentes en nuestra casuística fueron c.-32-13T>G, c.1799G>A y c.1082C>T. Conclusiones. Parecido a lo comunicado en publicaciones internacionales, la LOPD en México es clínicamente heterogénea; los pacientes pueden tardar años en llegar al diagnóstico. La debilidad muscular axial y proximal es el dato clínico más frecuente, por lo que la electromiografía debe incluir valoración de los músculos paraespinales. A excepción de una, las mutaciones encontradas en nuestra serie de casos se encuentran previamente descritas en las bases de datos de enfermedad de Pompe.
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Doença de Depósito de Glicogênio Tipo II , Doenças Musculares , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Doença de Depósito de Glicogênio Tipo II/genética , Humanos , México/epidemiologia , Mutação , Adulto Jovem , alfa-Glucosidases/genéticaRESUMO
Pompe disease (PD) is an autosomal recessive disorder by a deficiency of acid α-glucosidase (GAA) with intralysosomal glycogen accumulation in multiple tissues. We present the case of a 5-month-old male with hypertrophic cardiomyopathy, hypotony, feeding difficulties, and oxygen requirement since birth. At 3 months of age, he develops heart failure, respiratory impairment, and neurological deterioration. The echocardiogram revealed concentric hypertrophic cardiomyopathy with left-diastolic dysfunction. We found increased creatine-phosphokinase, lactate dehydrogenase, and urinary glucose tetrasaccharide levels, 50% of PAS-positive vacuolated lymphocytes in the peripheral blood smear, and low GAA activity. Sequencing of coding exons and flanking intronic sequences revealed a novel homozygous 4 bp deletion in exon 15 of the GAA gene (c.2066_2069delAGCC/p.Glu689Glyfs*6). IOPD was diagnosed. At 5 months old, we started enzyme replacement therapy with an alpha-alglucosidase of 20 mg/kg weekly and immunomodulation with intravenous immunoglobulin. He developed two cardiorespiratory arrests with subsequent neurologic deterioration, convulsive crisis, and respiratory failure and died at 9 months old. We found the usual PD hallmarks in the heart, striated muscle, and liver but also we found neuronal lesions characterized by cytoplasm vacuolization with PAS-positive granules in the central nervous system and myenteric plexus. We describe a novel GAA gene pathogenic variant with a particular phenotype characterized by classic IOPD and neurologic histopathological findings. Enhancing the knowledge of lysosomal diseases is critical to improving the diagnosis and treatment of these patients.
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Cardiomiopatia Hipertrófica , Doença de Depósito de Glicogênio Tipo II , Cardiomiopatia Hipertrófica/genética , Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/patologia , Humanos , Masculino , Músculo Esquelético/patologia , alfa-Glucosidases/genéticaRESUMO
PURPOSE: Current literature describes that art can be used to teach observation skills in medical students. In this way, many medical schools have developed formal observational training on works of art to improve their students' visual diagnostic skills. In this context, this description presents unprecedented evidence that Sandro Botticelli (1445-1510) may have represented a rare neuromuscular disorder, known as Pompe disease (accumulation of lysosomal glycogen primarily in the heart, skeletal muscles, and the nervous system) in one of the characters that make up Virgin and Child with the Infant St. John the Baptist (1490-1500). METHODS: Observational study. RESULTS: The painting reveals that the Infant Jesus has facial features consistent with some of the main clinical manifestations of Pompe disease (poor head control, facial weakness with open mouth posture, tongue protrusion, and eyelid ptosis). CONCLUSION: These results may indicate that Botticelli in 1500 may have made the first pictorial representation of Pompe's disease that was only described in the medical literature in 1932. Furthermore, this description demonstrates the importance of the medico-artistic field for the study of any disease during the Renaissance period, which will be essential for the learning process of visual diagnostic.
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Doença de Depósito de Glicogênio Tipo II , Criança , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Coração , Humanos , Lactente , Músculo Esquelético , ProtestantismoRESUMO
OBJECTIVE: To determine the outcomes of patients with later-onset Pompe disease (LOPD) identified through newborn screening (NBS). STUDY DESIGN: A prospective observational cohort study was conducted from the initiation of Pompe disease NBS by following subjects every 3-12 months for motor development and biochemical markers. RESULTS: Between 2005 and 2018, 39 of 994 975 newborns evaluated were classified as having LOPD based on low acid α-glucosidase (GAA) activity but no cardiac involvement at the time of screening. As of December 2020, 8 of these 39 infants (21%) were treated with enzyme replacement therapy owing to persistent elevation of creatine kinase (CK), cardiac involvement, or developmental delay. All subjects' physical performance and endurance improved after treatment. Subjects carrying c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] presented a phenotype of nonprogressive hypotonia, muscle weakness, and impairment in physical fitness tests, but they have not received treatment. CONCLUSIONS: One-fifth of subjects identified through NBS as having LOPD developed symptoms after a follow-up of up to 15 years. NBS was found to facilitate the early detection and early treatment of those subjects. GAA variants c.[752C>T;761C>T] and c.[546+5G>T; 1726G>A] might not cause Pompe disease but still may affect skeletal muscle function.
Assuntos
Doença de Depósito de Glicogênio Tipo II , Terapia de Reposição de Enzimas , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Doença de Depósito de Glicogênio Tipo II/terapia , Humanos , Recém-Nascido , Triagem Neonatal , Estudos Prospectivos , alfa-Glucosidases/genéticaRESUMO
Generalized glycogenosis is a lethal autosomal recessive disease caused by a deficient activity of the acidic 1,4-α-glucosidase enzyme and characterized by an accumulation of glycogen within lysosomes. Three mutations in the GAA gene causing bovine generalized glycogenosis have been identified in two cattle breeds, Brahman and Shorthorn. The objective of this study was to evaluate the prevalence of carriers of the E7 mutation in the GAA gene in Argentinean Brahman-derived herds. A total of 930 Braford, 94 Brangus, and 8 Brahman samples were analyzed. The genotyping was done by polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). We found that 12.02% (95% CI 12.00-12.04) of the total number of samples received were heterozygous (i.e., carriers) for the E7 mutation, while 12.58% (95% CI 12.56-12.60) of the Braford, 6.38% (95% CI 6.26-6.51) of the Brangus, and 12.50% (95% CI 9.82-15.18) of the Brahman samples were carriers of this loss-of-function allele. Neither breed nor sex were significantly associated to the presence of the mutation. The prevalence informed in this study is similar to the average prevalence reported for Australian Brahmans. The finding of heterozygous animals suggests that breeders and insemination centers should continue screening their herds to minimize the dissemination of this deleterious allele.
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Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Doença de Depósito de Glicogênio Tipo II/veterinária , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Animais , Argentina/epidemiologia , Bovinos , Feminino , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/epidemiologia , Masculino , PrevalênciaRESUMO
Pompe disease, also known as acid maltase deficiency or glycogenosis type II, is a rare severe, autosomal, recessive, and progressive genetic disorder caused by deficiency in alpha-glucosidase. The classic infantile-onset is the most broadly known form of Pompe disease, which presents with severe heart involvement and clear hypotonia, while the non-classic presentation occurs with early motor involvement. Late-onset Pompe disease develops in adults, but it may also occur during childhood or adolescence. Here we update the available clinical and diagnostic findings because an early management with enzyme replacement therapy may improve patients' survival and quality of life. We also review the benefits and adverse effects of available treatments and new lines of therapeutic research.
La enfermedad de Pompe, o deficiencia de maltasa ácida o glucogenosis tipo II, es una grave enfermedad genética, autosómica recesiva, progresiva, poco frecuente, causada por la deficiencia en la enzima alfa glucosidasa. En la edad pediátrica, puede presentarse con la "forma clásica", la más conocida, con grave compromiso cardíaco y franca hipotonía, o con la "forma no clásica", con comienzo temprano del compromiso motor. La "forma de comienzo tardío" del adulto también puede ocurrir en la infancia o en la adolescencia. Se actualizan los hallazgos clínicos y de diagnóstico disponibles, ya que un tratamiento temprano con reemplazo de la enzima faltante puede mejorar la supervivencia y la calidad de vida del paciente. Se revisan los beneficios y los efectos adversos del tratamiento disponible y nuevas líneas de investigación terapéutica.
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Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/terapia , Adolescente , Criança , Pré-Escolar , Doença de Depósito de Glicogênio Tipo II/complicações , Humanos , Lactente , Resultado do TratamentoRESUMO
Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase. In addition to the severe infantile form with cardiac involvement, late-onset variants can affect older children, adolescents (aged >1 year old) or adults. Patients with juvenile (a subgroup of late-onset type) Pompe disease typically do not have cardiac alterations e.g. hypertrophic cardiomyopathy, and the diagnosis is often difficult because it can clinically resemble myriad other neuromuscular disorders. A high level of clinical suspicion is necessary for a timely and accurate diagnosis. We describe 3 interesting cases of patients with juvenile-onset Pompe disease who presented some uncommon clinical features e.g. skeletal alterations and developmental delay, and describe a new genetic variant. Juvenile-onset Pompe disease may be accompanied by uncommon clinical signs that could delay the diagnosis of Pompe disease due to the global pictures resembling other metabolic disorders.
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Deficiências do Desenvolvimento/genética , Glucana 1,4-alfa-Glucosidase/genética , Doença de Depósito de Glicogênio Tipo II/genética , alfa-Glucosidases/genética , Adolescente , Deficiências do Desenvolvimento/diagnóstico , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/patologia , Humanos , Masculino , Músculo Esquelético/patologia , Mutação/genéticaRESUMO
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.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumologia/métodos , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Teste em Amostras de Sangue Seco/normas , Transtornos de Início Tardio/diagnóstico , Pneumopatias/complicações , Biópsia , Doença de Depósito de Glicogênio Tipo II/sangue , Doença de Depósito de Glicogênio Tipo II/enzimologia , Diagnóstico Precoce , alfa-Glucosidases/metabolismo , Transtornos de Início Tardio/sangue , Transtornos de Início Tardio/enzimologia , Itália , Pneumopatias/sangue , Músculos/cirurgia , Músculos/enzimologiaRESUMO
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.
Assuntos
Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/terapia , Idade de Início , Argentina , Prova Pericial , Doença de Depósito de Glicogênio Tipo II/complicações , HumanosRESUMO
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.
Assuntos
Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/terapia , Argentina , Doença de Depósito de Glicogênio Tipo II/complicações , Idade de Início , Prova PericialRESUMO
Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with "unexplained" limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an "unexplained" limb-girdle weakness even without vacuolar myopathy in muscle biopsy.
Assuntos
Doença de Depósito de Glicogênio Tipo II/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/sangue , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , alfa-Glucosidases/sangue , Adulto , Biópsia , Feminino , Doença de Depósito de Glicogênio Tipo II/sangue , Doença de Depósito de Glicogênio Tipo II/patologia , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/patologia , PrevalênciaRESUMO
ABSTRACT Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with "unexplained" limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an "unexplained" limb-girdle weakness even without vacuolar myopathy in muscle biopsy.
RESUMO A doença de Pompe é uma doença hereditária causada pela deficiência da enzima alfa-glicosidase ácida (GAA). Estudo observacional foi realizado, em um único centro, para determinar a prevalência da doença de Pompe de início tardio (LOPD) em uma população brasileira de alto risco, usando teste em gota seca (DBS) como ferramenta principal de triagem para detectar a deficiência da GAA. DBS foi coletado para avaliar a atividade da GAA em 24 pacientes com fraqueza muscular de cinturas "não explicada" sem miopatia vacuolar na biópsia muscular. As amostras com atividade enzimática reduzida foram também submetidas a análise de mutações no gene GAA. Dos 24 pacientes com DBS, baixa atividade da enzima GAA (NaG/AaGIA: 40.42; %INH: 87.22%) foi encontrada em um paciente (4.2%). Nessa paciente, a análise genética confirmou duas mutações em heterozigose composta no gene GAA (c.-32-13T > G/p.Arg854Ter). Nossos resultados confirmam que LOPD deve ser investigada quando a manifestação clínica é uma fraqueza muscular de cinturas "não explicada", mesmo na ausência de miopatia vacuolar na biópsia muscular.
Assuntos
Humanos , Masculino , Feminino , Adulto , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/sangue , alfa-Glucosidases/sangue , Biópsia , Doença de Depósito de Glicogênio Tipo II/patologia , Doença de Depósito de Glicogênio Tipo II/sangue , Prevalência , Distrofia Muscular do Cíngulo dos Membros/patologiaRESUMO
Glycogen storage disease type II, also known as Pompe disease, is an autosomal recessive disorder caused by deficiency of enzymatic activity of acid alpha-glucosidase. The wide phenotypical variation of this disease relates to the amount of residual enzymatic activity depending on the combination of mutations on each allele. We confirmed Pompe disease in a patient that presented with progressive weakness, recurrent episodes of respiratory failure associated with pneumonia, a predominantly demyelinating mixed sensorimotor polyneuropathy and paraspinal complex repetitive discharges. Genetic analysis of the GAA gene from this patient revealed two pathogenic compound heterozygous mutations: c.-32-13T>G (rs386834236, intronic), c.2560C>T (rs121907943, p.Arg854Ter); and one variant of unknown significance: c.1551+42G>A (rs115427918, intronic). We found expected mutations in two siblings and two nieces. Genetic variants reported in this family reflect on the European and African ancestry that we carry in our Costa Rican population.
Assuntos
Predisposição Genética para Doença , Doença de Depósito de Glicogênio Tipo II/genética , Mutação/genética , alfa-Glucosidases/genética , Idade de Início , Costa Rica , Estudos de Associação Genética , Testes Genéticos/métodos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Objective: To describe respiratory function in a series of patients with late-onset Pompe disease after the definitive diagnosis and before enzyme replacement therapy. Methods: This was a cross-sectional study involving patients with a definitive molecular diagnosis of late-onset Pompe disease. The data analyzed included age at symptom onset; age at definitive diagnosis; type of initial symptoms; time from symptom onset to diagnosis; FVC in the sitting and supine positions; six-minute walk distance; and locomotor ability. Analyses were carried out using frequencies, medians, minimum values, and maximum values. Results: Six patients were included in the study. The median age at symptom onset was 15 years (range, 13-50 years), and the median age at diagnosis was 39.5 years (range, 10-64 years). The median time from symptom onset to diagnosis was 8 years (range, 0-45 years). In all cases, the initial manifestation of the disease had been motor weakness. The median FVC in percentage of the predicted value (FVC%) in the sitting and supine positions was 71.0% (range, 22.9-104.6%) and 58.0% (range, 10.9-106.9%), respectively. The median ΔFVC% was 24.5% (range, -4.59 to 52.40%).The median six-minute walk distance was 391.7 m (range, 97-702 m) . Conclusions: In this case series, the time from symptom onset to diagnosis was long. Although respiratory signs or symptoms were not the initial manifestations of the disease, 66.7% of the patients showed reduced FVC% in the sitting and supine positions at diagnosis.
Objetivo: Descrever a função respiratória em uma série de pacientes com doença de Pompe de início tardio após o diagnóstico definitivo e antes do início do tratamento através de terapia de reposição enzimática. Métodos: Estudo transversal em pacientes com diagnóstico molecular de doença de Pompe de início tardio. As informações analisadas incluíram idade ao início dos sintomas e ao diagnóstico, tipo de sintoma inicial, tempo entre início dos sintomas e diagnóstico, CVF em posição sentada e supina, distância percorrida no teste de caminhada de seis minutos e capacidade de locomoção. Análises por frequência, mediana, valor mínimo e valor máximo foram realizadas. Resultados: Foram incluídos seis pacientes no estudo. A mediana de idade ao início dos sintomas foi de 15 anos (variação, 13-50 anos) e a de idade ao diagnóstico foi de 39,5 anos (variação, 10-63 anos). A mediana de tempo entre o início dos sintomas e a confirmação diagnóstica foi de 8 anos (variação, 0-45 anos). A manifestação inicial da doença foi de sintomas motores de fraqueza muscular em todos os casos. As medianas da CVF em porcentagem do previsto (CVF%) em posição sentada, em supino e ΔCVF% foram de, respectivamente, 71,0% (variação, 22,9-104,6%), 58,0% (variação, 10,9-106,9%) e 24,5% (-4,59 a 52,40%). A mediana da distância percorrida no teste de caminhada de seis minutos foi de 391,7 m (variação, 97-702 m). Conclusões: Nesta série, o tempo entre o início dos sintomas e o diagnóstico foi longo. A manifestação inicial da doença não foi de sinais ou sintomas respiratórios, embora 66,7% dos pacientes apresentassem redução da CVF% em posição sentada e em supino no momento do diagnóstico.