ABSTRACT
La enfermedad de Tay-Sachs es una enfermedad metabólica hereditaria neurodegenerativa. Existen cuatro tipos según el inicio de los síntomas clínicos: infantil, infantil de inicio tardío, juvenil y adulto. El tipo infantil tiene el peor pronóstico. Recientemente, se describieron diferentes anomalías que acompañan a los trastornos metabólicos e influyen en el pronóstico. Presentamos el caso de un lactante con enfermedad de Tay-Sachs junto con coartación aórtica y reflujo vesicoureteral bilateral (RVU) de grado V. Se realizó el seguimiento del paciente en el consultorio externo de Cardiología Pediátrica. En la ecografía abdominal, se observó ectasia pielocalicial, y se detectó reflujo vesicoureteral bilateral de grado V en la cistouretrografía miccional. No se ha informado previamente la coexistencia de estas anomalías. Este caso pone de manifiesto que no se deben subestimar las anomalías del examen neurológico en los pacientes con una cirugía cardíaca reciente, porque podría perderse la oportunidad de diagnosticar enzimopatías congénitas.
Tay-Sachs disease is a neurodegenerative inherited metabolic disease. There are four forms classified by the time of first clinical symptoms: infantile, late infantile, juvenile and adult. Infantile form has the poorest prognosis. Lately, different abnormalities which accompany metabolic disorders and affect the prognosis have been described. We present an infant with Tay-Sachs disease accompanied by coarctation of the aorta and bilateral grade V vesicoureteral reflux (VUR). The patient was followed up in the outpatient clinic of Pediatric Cardiology. The abdominal ultrasonography showed pelvicalyceal ectasia; bilateral grade V VUR in voiding cystourethrography was found. This coexistence has not been previously reported. This case emphasizes that abnormalities in the neurological examination of cardiac postsurgical patients should not be underestimated because the opportunity to diagnose inborn errors of metabolism could be missed.
Subject(s)
Humans , Male , Infant , Aortic Coarctation/complications , Aortic Coarctation/diagnosis , Tay-Sachs Disease/diagnosis , Vesico-Ureteral Reflux/complications , Vesico-Ureteral Reflux/diagnosisABSTRACT
Tay–Sachs disease (TSD), a deficiency of b-hexosaminidase A (Hex A), is a rare but debilitating hereditary metabolic disorder. Symptoms include extensive neurodegeneration and often result in death in infancy. We report an in silico study of 42 Hex A variants associated with the disease. Variants were separated into three groups according to the age of onset: infantile (n=28), juvenile (n=9) and adult (n=5). Protein stability, aggregation potential and the degree of conservation of residues were predicted using a range of in silico tools. We explored the relationship between these properties and the age of onset of TSD. There was no significant relationship between protein stability and disease severity or between protein aggregation and disease severity. Infantile TSD had a significantly higher mean conservation score than nondisease associated variants. This was not seen in either juvenile or adult TSD. This study has established that the degree of residue conservation may be predictive of infantile TSD. It is possible that these more highly conserved residues are involved in trafficking of the protein to the lysosome. In addition, we developed and validated software tools to automate the process of in silico analysis of proteins involved in inherited metabolic diseases. Further work is required to identify the function of well-conserved residues to establish an in silico predictive model of TSD severity
ABSTRACT
Abstract Introduction: Lysosomal storage disease is caused by the deficiency of a single hydrolase (lysosomal enzymes). GM2 gangliosidoses are autosomal recessive disorders caused by deficiency of β-hexosaminidase and Tay-Sachs disease (TSD) is one of its three forms. Objective: To perform a review of the state of the art on TSD and describe its definition, epidemiology, etiology, physiopathology, clinical manifestations, as well as advances regarding its diagnosis and treatment. Materials and methods: A literature search was carried out in PubMed using the MeSH terms "Tay-Sachs Disease". Results: after the initial search was conducted, 1 233 results were retrieved, of which 53 articles were finally selected. TSD is caused by the deficiency of the lysosomal enzyme β-hexosaminidase A (HexA), and is characterized by neurodevelopmental regression, hypotonia, hyperacusis and cherry-red spots in the macula. Research on molecular pathogenesis and the development of possible treatments has been limited, consequently there is no treatment established to date. Conclusion: TSD is an autosomal recessive neurodegenerative disorder. Death usually occurs before the age of five. More research and studies on this type of gangliosidosis are needed in order to find an adequate treatment.
Resumen Introducción. La deficiencia de una sola hidrolasa (enzimas lisosomales) da como resultado una enfermedad de almacenamiento lisosomal. Las gangliosidosis GM2 son trastornos autosómicos recesivos causados por la deficiencia de β-hexosaminidasa. La enfermedad de Tay-Sachs (TSD, por sus siglas en inglés) es una de las tres presentaciones de este tipo de gangliosidosis. Objetivo. Realizar una revisión del estado del arte de la TSD describiendo su definición, epidemiología, etiología, fisiopatología, manifestaciones clínicas y actualidades en su diagnóstico y tratamiento. Materiales y métodos. Se realizó una búsqueda bibliográfica en PubMed utilizando como único término MeSH "Tay-Sachs Disease". Resultados. Se encontraron 1 233 publicaciones y se seleccionaron 53 artículos. La TSD es originada por la deficiencia de la enzima lisosomal β-hexosaminidasa A (HexA) y se caracteriza por regresión del neurodesarrollo, hipotonía, hiperacusia y manchas maculares rojo cereza. La investigación de la patogenia molecular y el desarrollo de posibles tratamientos han sido limitados y en la actualidad no se cuenta con uno plenamente establecido. Conclusiones. La TSD es un trastorno neurodegenerativo autosómico recesivo y por lo general la muerte se produce antes de los 5 años de edad. Son necesarias más investigaciones y estudios sobre este tipo de gangliosidosis con el fin de encontrar un tratamiento adecuado.
ABSTRACT
BACKGROUND AND PURPOSE: Antiganglioside antibodies are known to play a pathogenic role in Guillain-Barré syndrome (GBS). Either an immunoglobulin (Ig)G- or IgM-type anti-GM2 antibody is detected in rare cases in GBS patients. However, the specific pathogenic role of these antibodies in GBS has not been reported previously. This study aimed to define and characterize the clinical spectrum of GBS with anti-GM2 positivity. METHODS: We reviewed the database of the Dong-A University Neuroimmunology Team, which has collected sera of GBS and its variants from more than 40 general and university-based hospitals in Korea. Detailed information about the involved patients was often obtained and then corrected by the charge doctor applying additional questionnaires. RESULTS: Four patients with acute monophasic peripheral neuropathy or cranial neuropathy with isolated IgM-type anti-GM2-antibody positivity were recruited. In addition, IgG-type anti-GM2 antibody was solely detected in the sera of another four patients. The IgM-positive group comprised heterogeneous syndromes: two cases of acute motor axonal neuropathy, one of acute inflammatory demyelinating polyneuropathy, and one of isolated facial diplegia. In contrast, all of the cases enrolled in the IgG-positive group manifested with dizziness with or without oculomotor palsy due to cranial neuropathy syndrome. CONCLUSIONS: This study has identified that anti-GM2 antibody can be found in various subtypes of GBS and its variants in rare cases. Compared to the clinical heterogeneity of the IgM-positive group, the IgG-positive group can be characterized by cranial-dominant GBS variants presenting mainly with oculomotor and vestibular dysfunctions.
Subject(s)
Humans , Antibodies , Axons , Cranial Nerve Diseases , Dizziness , Guillain-Barre Syndrome , Immunoglobulins , Korea , Paralysis , Peripheral Nervous System Diseases , Population CharacteristicsABSTRACT
La enfermedad de Sandhoff es una patología neurodegenerativa, de almacenamiento lisosomal, causada por mutaciones en el gen HEXB. Existen tres formas clínicas: infantil, juvenil y adulta. Previamente, fue identificada una población endogámica en la provincia de Córdoba, Argentina, que presentaba una alta incidencia de la enfermedad; todos los casos correspondieron a la forma infantil. En este trabajo, se presenta por primera vez el caso de un paciente argentino con la variante juvenil de la enfermedad de Sandhoff. El paciente es un niño de 7 años que, a partir de los 2, presentó ataxia, trastorno del habla y retraso global en el desarrollo. El diagnóstico se confirmó con la detección de valores residuales de enzima hexosaminidasa y con la identificación de dos mutaciones ya descritas en estado de heterocigosis: c.796T>G (p.Y266D) y c.1615C>T (p.R539C).
Sandhoff disease is a neurodegenerative, lysosomal and autosomal recessive disease caused by mutations in the HEXB gene. Three forms are recognized: infantile, juvenile and adult. Previously, an endogamous population in Córdoba, Argentina, was identified with a high incidence of Sandhoff disease, all reported cases were of the infantile type. In this work, we describe a child with the juvenile form of Sandhoff disease, the first case reported in Argentina. The patient is a 7-year-old boy presenting with ataxia, speech disturbances and global developmental delay, symptoms starting at the age of 2 years. Diagnosis was based on the hexosaminidase deficiency. Sequencing of genomic DNA revealed compound heterozygosity for two HEXB gene mutations: c.796T>G (p.Y266D) and c.1615C>T (p.R539C), both already reported.
Subject(s)
Humans , Male , Child , Sandhoff Disease/diagnosis , Argentina , Sandhoff Disease/classificationABSTRACT
Las gangliosidosis son un conjunto de enfermedades hereditarias de almacenamiento lisosómico, debidas a un acúmulo de gangliósidos, sobre todo en las neuronas. La causa es la disfunción de alguna de las enzimas lisosómicas de la ruta de degradación de los gangliósidos. Existen varias formas de gangliosidosis, como son la GM1 y GM2. Se presentó el caso de una paciente de 33 años de edad, que había sido diagnosticada anteriormente de esclerosis lateral amiotrófica. Por varios síntomas presentados se le realizan una serie de exámenes complementarios, los cuales arrojan como resultado una gangliosidosis GM-2 tipo II o enfermedad de Sandhoff.
Gangliosidosis are a group of hereditary diseases of lysosomal storage, due to an accumulation of gangliosides, especially in the neurons. The cause is the dysfunction of several lysosomal enzymes in the way of the gangliosides degradation. There are several forms of gangliosidesis, like GM1 and GM2. We present the case of a 33-years-old patient who was previously diagnosed with lateral amyotrophic sclerosis. Because of several symptoms he presented we carried out some complementary exams showing as a result a gangliosidosis GM-2 Type II or Sandhoff disease.
ABSTRACT
La enfermedad de Tay-Sachs es un trastorno neurodegenerativo progresivo de herencia autosómica recesiva. Se debe a la deficiencia de la enzima β-hexosaminidasa A, que provoca una acumulación de gangliósidos GM2 en los lisosomas. Se incluye dentro de las esfingolipidosis. De las esfingolipidosis que presentan mancha rojo cereza en la mácula, la enfermedad de Tay-Sachs es la única en la que no se evidencia hepatoesplenomegalia. La variante más frecuente se inicia en la lactancia. Se presenta un lactante del sexo masculino al que se le realizó el diagnóstico de esta entidad a los 8 meses de edad. A partir de los 4 meses comenzó a presentar una reacción de sobresalto. A los 6 meses comenzó a perder habilidades previamente adquiridas y crisis epilépticas mioclónicas. Se constató una disminución de la actividad específica de la enzima hexosaminidasa A en leucocitos.
Tay-Sachs disease is a progressive autosomal recessive inherited neurodegenerative disorder caused by Beta-hexosaminidase A enzyme deficiency that in turn provokes GM2 ganglioside accumulation in the lysosomes. It is included in the sphyngolipidoses classification. Among the sphyngolipidoses that present with cherry-red spot in the macula, Tay-Sachs disease is the only one that does not show hepatosplenomegaly. The most frequent variant begins at the breast-feeding phase. This report presented a male nursling who was diagnosed with Tay-Sachs disease at the age of 8 months. At 4 months of age, he had begun getting some fright reactions. At 6 months-old, he began losing his previously acquired skills and suffering myoclonic seizures. The cause was the reduced specific activity of the hexosaminidase A enzyme in leukocytes.
Subject(s)
Humans , Male , Tay-Sachs Disease/complications , Tay-Sachs Disease/diagnosis , Hexosaminidase AABSTRACT
Tay-Sachs disease is an autosomal recessive disorder of sphingolipid metabolism, caused by enzime hexosaminidase A deficiency that leads to an accumulation of GM2 in neurocytes which results in progressive loss of neurological function. The accumulation of lipid in retinal ganglion cells that leads to a chalk-white appearance of the fundus called "cherry red spot" is the hallmark of Tay-Sachs disease. It is also seen in others neurometabolic diseases as well as in central retinal artery occlusion. This case reports a child with Tay-Sachs disease in a family with four previous similar deaths without diagnostic.
Tay-Sachs é uma doença autossômica recessiva, caracterizada pela deficiência da enzima hexosaminidase A levando ao acúmulo de esfingolipídios (GM2) em células neuronais que resulta em uma perda progressiva da função neurológica. O acúmulo de lipídios em células ganglionais da retina leva a uma aparência de mácula em cereja, característica do fundo de olho de pessoas acometidas. "Mácula em cereja" também pode ser vista em outras doenças neurometabólicas e em oclusão da artéria central da retina. Este trabalho relata o caso de um paciente com doença de Tay-Sachs em uma família com história de quatro óbitos por causas semelhantes sem diagnóstico.
Subject(s)
Humans , Infant , Male , Macula Lutea/pathology , Retinal Diseases/diagnosis , Tay-Sachs Disease/diagnosis , Ophthalmoscopy , Retinal Diseases/etiology , Tay-Sachs Disease/complicationsABSTRACT
Tay-Sachs Disease (TSD), the most common form of GM(2) gangliosidosis, is an autosomal recessive inborn lysosomal glycosphingolipid storage disease which is resulted from the mutations that affect the alpha-subunit locus on chromosome 15 and cause a severe deficiency of hexosaminidase A. It is characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 6 months of life. Neurodegeneration is relentless and manifested as relentless motor and mental deterioration, beginning with motor incoordination, mental obtundation leading to muscular flaccidity, blindness, and increasing dementia, with death occurring by the age of 4 or 5 years. We report a successful anesthetic management in a patient with Tay-Sachs Diseases for tracheostomy and feeding gastrostomy.
Subject(s)
Humans , Ataxia , Blindness , Chromosomes, Human, Pair 15 , Dementia , Gangliosidoses , Gastrostomy , Hexosaminidase A , Hexosaminidases , Motor Skills , Muscle Hypotonia , Tay-Sachs Disease , TracheostomyABSTRACT
Sphingolipidoses are a subgroup of lysosomal storage disorders. They are characterized by relentless progressive storage in affected organs and concomitant functional impairments. No overall screening procedure for these disorders is available. Their course and appearance, however, are usually characteristic and, together with relevant technical procedures such as magnetic resonance imaging (MRI), clinical neurophysiology, ophthalmologic examination, etc., a provisional diagnosis can be made, after which enzymatic diagnosis can close the gap in the diagnostic process. Subgroups of sphingolipidoses are grouped together, such as disorders with prominent hepatosplenomegaly (Niemann-Pick A, B and Gaucher disease) and disorders with central and peripheral demyelination (metachromic leukodystrophy and Krabbe disease). Farber disease and Fabry disease are unique in themselves. The last decade has seen hopeful progress in therapeutic strategies, especially for Gaucher disease. Therefore, emphasis of this review has been placed on these new developments.
Subject(s)
Demyelinating Diseases , Diagnosis , Fabry Disease , Farber Lipogranulomatosis , Gangliosidoses, GM2 , Gangliosidosis, GM1 , Gaucher Disease , Hope , Leukodystrophy, Globoid Cell , Magnetic Resonance Imaging , Mass Screening , Neurophysiology , Niemann-Pick Diseases , SphingolipidosesABSTRACT
GM2 gangliosidosis II(Sandhoff disease) is a lysosomal storage disease due to deficiency of beta-hexosaminidase activity, transmitted by mode of autosomal recessive. Clinical features are so variable, ranging from infantile onset resulting death before 4 years, to subacute or chronic forms with more slowly progressive neurologic condition. We experienced a case of GM2 gangliosidosis II in a 14 months old male who had developmental deterioration and seizures, so we report and review the related literatures.
Subject(s)
Humans , Infant , Male , beta-N-Acetylhexosaminidases , Gangliosidoses, GM2 , Hexosaminidases , Lysosomal Storage Diseases , SeizuresABSTRACT
The investigation on distribution of Gm(2)facotor in 269 Chinese people living in Beijing was carried out using haemagglutination inhibition test and anti-Gm(2)sera from the Biotest Diagnosis of West Germany.Results revealed that Gm(2)factors was positive in 78 cases(29%),while negative in 191 cases(71%).Gm(2)phenotyping were(?)erformed successfully in 230 bloodstains, 14 months old,made of fresh blood selected from 269 samples of known Gm(2) phenotype.Detection of Gm(2)factors was carried out in 11 crime cases.Sus- pects were excluded in 4 cases.