Papers by norberto antongiovanni
Kidney international reports, Apr 1, 2024
Revista de Nefrología, Diálisis y Trasplante, 2019
Introduction: Vascular events (VE), both cardiovascular (CVD) and cerebrovascular (CVA), are the ... more Introduction: Vascular events (VE), both cardiovascular (CVD) and cerebrovascular (CVA), are the main cause of death in patients with Fabry disease (FD). The aim of this study was to describe the occurrence of VE in patients with FD and end-stage renal disease (ESRD) on hemodialysis during follow-up. Methods: a retrospective, cohort study was carried out at three centers in Argentina between January 2010 and January 2017. Hemodialysis patients with FD and ESRD were included. Information was collected regarding demographic, clinical and VE aspects. Results: Eight adult (40 ± 4.2 year-old) male patients with ESRD on hemodialysis (mean time on dialysis: 39.1 ± 20.6 months) were included; the mean followup time was 55 ± 12 months. Five patients received enzyme replacement therapy during follow-up. Four patients (50%) had VE during follow-up. In three of them the cardiovascular event was fatal. The mean time from admission to dialysis until the onset of VE was 38 ± 8 months. Conclusion: ...
International Journal of Clinical Practice, 2012
Revista de Nefrología, Diálisis y Trasplante, 2014
Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase... more Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase A enzyme that causes a pathological accumulation of glycosphingolipids mainly in the endothelial cells, vascular smooth muscle cells and podocytes among others. Enzyme replacement therapy is the only option for a specific treatment at present. Increasing knowledge of the physiopathological mechanisms has changed the management of the disease and above all, when treatment should begin. At present, beginning treatment at an early age seems to be a way of preventing and in some cases reverting some of the signs and symptoms of Fabry disease.
Revista de Nefrología, Diálisis y Trasplante, 2017
Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or d... more Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. Co...
Revista De Nefrologia Dialisis Y Trasplante, 2017
Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or d... more Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. C...
Medicina-buenos Aires, 2013
: Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the ... more : Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.
Se presenta una mujer de 42 anos de edad con agenesia renal congenita y enfermedad de Fabry, una ... more Se presenta una mujer de 42 anos de edad con agenesia renal congenita y enfermedad de Fabry, una asociacion no comunicada hasta la fecha. Ambas patologias son posibles causas de proteinuria. Por la contraindicacion relativa que significa la presencia de rinon unico no se realizo biopsia renal y la paciente normaliza la albuminuria con tratamiento de reemplazo enzimatico. La realizacion de biopsia renal hubiera significado aclarar la causa de la albuminuria, aunque la respuesta favorable al tratamiento especifico de la enfermedad de Fabry (EF) podria hacer sospechar que la EF fue la causa de esta. El proposito del presente trabajo es comunicar una asociacion de dos patologias renales poco frecuentes y generar discusion sobre la necesidad de contar con biomarcadores de nefropatia, obtenidos por metodos no invasivos y factibles de realizar en la practica medica habitual, para mejorar el manejo del compromiso renal por enfermedad de Fabry. Palabras clave. Enfermedad de Fabry, agenesia ...
Varon de 32 anos derivado por proteinuria e HTA. Antecedentes: ACV isquemico, acroparestesias, in... more Varon de 32 anos derivado por proteinuria e HTA. Antecedentes: ACV isquemico, acroparestesias, intolerancia al calor y ejercicio. Madre: cardiopatia isquemica, HTA y microalbuminuria. Examen fisico: angiokeratomas. Laboratorio: Creatinina: 2,1 mg/dl y proteinuria 4,9 g/24 Hs. Ecocardiograma compatible con cardiopatia hipertensiva. RMN de SNC: lesion isquemica secuelar. Biopsia Renal: compatible con Enfermedad de Fabry. Se confirmo dicho diagnostico mediante dosaje enzimatico y estudio genetico. Estudio genetico materno normal. La Enfermedad de Fabry es una enfermedad ligada al cromosoma X resultante de la deficiente actividad a-galactosidasa-A, esto genera acumulacion progresiva de glicoesfingolipidos en los lisosomas de numerosas estirpes celulares. Existen mas de 1.000 mutaciones del gen GLA. Se describe el caso de una mutacion de novo con la particularidad de tener su madre fenotipo compatible con Enfermedad de Fabry, patologia ligada al cromosoma X, sin encontrarse mutacion en l...
Introduction: Vascular events (VE), both cardiovascular (CVD) and cerebrovascular (CVA), are the ... more Introduction: Vascular events (VE), both cardiovascular (CVD) and cerebrovascular (CVA), are the main cause of death in patients with Fabry disease (FD). The aim of this study was to describe the occurrence of VE in patients with FD and end-stage renal disease (ESRD) on hemodialysis during follow-up. Methods: a retrospective, cohort study was carried out at three centers in Argentina between January 2010 and January 2017. Hemodialysis patients with FD and ESRD were included. Information was collected regarding demographic, clinical and VE aspects. Results: Eight adult (40 ± 4.2 year-old) male patients with ESRD on hemodialysis (mean time on dialysis: 39.1 ± 20.6 months) were included; the mean followup time was 55 ± 12 months. Five patients received enzyme replacement therapy during follow-up. Four patients (50%) had VE during follow-up. In three of them the cardiovascular event was fatal. The mean time from admission to dialysis until the onset of VE was 38 ± 8 months. Conclusion: ...
more common as they appear routinely in different populations. To identify them, we analysed the ... more more common as they appear routinely in different populations. To identify them, we analysed the genotypes of MPS-I patients from thirty-five papers and calculated the frequency of every allele for each country. Additionally, Genome Aggregation Database (gnomAD) was consulted to evaluate the allele occurrence in healthy individuals. The most common mutations observed in MPS I patients were p.Trp402Ter, p.Gln70Ter and p.Pro533Arg. The first is the major allele in central Europe, in countries as Spain, Germany, Netherlands, Czech Republic and Slovakia and in the United Kingdom. From its distribution in Europe, we suggest that it has originated possibly with the Celts that once inhabited the continent, further reaching Americas and Australia with 15th century European's navigations. p.Gln70Ter's is very frequent in Finland, Norway and Russia, rareing further south. From its distribution, we suggest a possible Viking origin: they inhabited Scandinavia and migrated towards other European regions in the 8th century. United States and Australia inherited this allele with later British colonization. Finally, p.Pro533Arg is very frequent in Morocco, Algeria and Tunisia. It is also present in Spain, Italy and Turkey, meanwhile rare in Northern Europe. Considering these frequencies, we suggest that p.Pro533Arg originated in North Africa and spread towards Mediterranean countries with Moorish conquests in the Middle Age. South Europeans eventually migrated to Latin America, justifying the high frequency observed in Mexico and Brazil. Data from gnomAD mirrors what was observed in MPS-I patients. In conclusion, the distribution of the three most common IDUA mutations (p.Trp402Ter, p.Gln70Ter and p.Pro533Arg) varies around the world, with possibly different origins. This knowledge facilitates the design of new therapies based on the genotype, but also helps in fast diagnosis and, consequently, better treatment outcomes. Funding: CNPq
espanolLa Enfermedad de Fabry (EF) es una enfermedad hereditaria ligada al cromosoma X resultante... more espanolLa Enfermedad de Fabry (EF) es una enfermedad hereditaria ligada al cromosoma X resultante de la deficiencia o ausencia de actividad enzimatica α-galactosidasa A, este deficit genera acumulacion progresiva de globo triaocilceramida y otros glicoesfin golipidos, en los lisosomas de diferentes estirpes celulares, entre ellas, las del parenquima renal. Los pacientes afectados desarrollan insuficiencia renal, cardiaca, y tambien accidentes cerebrovasculares, con morbimortalidad aumentada y disminucion de la expectativa de vida. El compromiso renal es frecuente en los pacientes de ambos sexos, habiendo sido la principal causa de muerte en la etapa previa a la aparicion de las terapias de reemplazo de la funcion renal. El trasplante renal debe ser considerado tempranamente en los pacientes con Enfermedad Renal Cronica Terminal. Considerando la importancia que el trasplante renal tiene en pacientes con EF, el objetivo del presente trabajo es llevar a cabo una revision sobre los aspe...
Introduccion. Los criterios de indicacion de tratamiento en enfermedades lisosomales son motivo d... more Introduccion. Los criterios de indicacion de tratamiento en enfermedades lisosomales son motivo decontroversia. La deteccion temprana de sintomas posibilitaria un inicio temprano de tratamiento y mejorariael pronostico de pacientes afectados, aunque esto es dificultoso, por su presentacion clinica variable.Objetivo. Analizar los criterios de indicacion de tratamiento de pacientes con enfermedad de Fabry(EF). Material y metodos. Estudio observacional, de diseno transversal. Resultados. Se incluyo a 73pacientes (26,43 ± 16,54 anos); 31 varones y 42 mujeres; 24 pediatricos y 49 adultos; de 14 genotipos.15 pacientes caso indice (CI); 13 varones y 2 mujeres; todos tuvieron indicacion de tratamiento. No huboCI pediatricos. De 26 pacientes “no casos indice” (no CI), 17 fueron adultos (7 varones; 10 mujeres) y9 pediatricos (5 varones; 4 mujeres). En la poblacion CI solo un paciente no presento manifestacionestardias de la EF como criterio de iniciacion de tratamiento; su indicacion fue comp...
Introduction: Periodontal disease (PD), the main cause of tooth loss in adults, comprises a serie... more Introduction: Periodontal disease (PD), the main cause of tooth loss in adults, comprises a series of conditions of infectious etiology that can produce chronic inflammation. Objective: To determine the oral, particularly periodontal, health condition in chronic hemodialysis (CHD) patients. Methods: This is a descriptive, crosssectional study in CHD patients. The oral examination was performed by a certified odontologist in the dialysis unit, together with a C-reactive protein (CRP) assessment. Demographic data, diabetic and non-diabetic etiology, smoking, body mass index, erythropoietin use and health coverage information has been provided in tabulated form. Patients were divided into PD and non-PD groups. Results: 65 patients took part: 67.6% were male, 13.8 % diabetic, mean age of 60.6+16.5, mean time on CHD 60.8+53.5. Forty one patients were diagnosed with PD (63.1%), only 5 had a normal oral examination; 8 patients had caries (12%), 12 had prosthesis (18.5%) (5 with complete su...
Nefrología Latinoamericana, 2017
Resumen Introduccion La enfermedad de Fabry (EF) es un trastorno de deposito lisosomal, ligado al... more Resumen Introduccion La enfermedad de Fabry (EF) es un trastorno de deposito lisosomal, ligado al cromosoma X, resultante de la deficiencia o ausencia de la enzima alfa galactosidasa A (α-galA). El compromiso organico en los hombres es bien conocido, pero en las mujeres es motivo de controversia, debido en parte al fenomeno de lionizacion. El objetivo de este estudio fue describir el compromiso renal en una poblacion de 35 mujeres en el momento del diagnostico de la EF. Metodo Se evaluaron 35 mujeres de 3 centros de referencia de Argentina. La actividad de la enzima α-galA se realizo en papel de filtro por metodo fluorometrico y el estudio mutacional mediante MLPA y secuenciacion. Se calculo la tasa de filtrado glomerular por formula CKD-EPI en pacientes adultos y Schwartz en pediatricos. Se considero albuminuria y proteinuria en al menos 2 muestras diferentes de orina en todos los casos, y a las categorias del filtrado glomerular segun guias KDIGO 2012. Resultados El promedio de ed...
Nephro-Urology Monthly, 2020
Background: Fabry disease is a genetic disorder caused by the deficiency of the lysosomal α-galac... more Background: Fabry disease is a genetic disorder caused by the deficiency of the lysosomal α-galactosidase A enzyme. This failure generates the storage of globotriaosylceramide in different cells with a progressive multi-organ involvement. Objectives: To report the prevalence of glomerular hyperfiltration in Fabry disease patients and the association with clinical variables. Methods: Adult patients (≥ 18 years) at the moment of FD diagnosis were evaluated. The variables studied were: central and peripheral nervous system compromise, presence of arterial hypertension, cardiac arrhythmia, left ventricular hypertrophy, albuminuria/proteinuria, cornea verticillata, gastrointestinal involvement, treatment with inhibitors of the renin-angiotensin-aldosterone system, deafness, and presence of angiokeratomas. Results: Forty-eight adults with Fabry disease (35.9 ± 11.7 years), 28 women (58.3%), and 20 men (41.7%) were analyzed. Nine (18.8%) patients with glomerular hyperfiltration, including ...
The Scientific World Journal, 2018
Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the deficiency or abs... more Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the alpha galactosidase A enzyme. Organic involvement in men is well known, but in women it is controversial, partly due to the random X-chromosomes inactivation (Lyon hypothesis). The aim of this study was to describe the organic involvement in women at the time of FD diagnosis. A descriptive, cross-sectional and multicenter study was carried out. Thirty-five women with FD from three reference centers in Argentina were evaluated. The mean age of the whole group (n=35) was 26.6±16.9 years; 22 were adult (over 18) and 13 were paediatric patients. Enzymatic activity was performed in 29/35 patients, which was normal in 24/29 (82.8%). Seven different mutations of the GLA gene were found. The results showed urinary protein loss (45.7%) and decreased glomerular filtration rate (31.4%), mainly in adults. And also, cornea verticillata (56.5%), peripheral neuropathy (51.4%), cardiovascula...
Indian Journal of Nephrology, 2019
Introduction: Nephropathy is one of the major complications of Fabry disease and mainly includes ... more Introduction: Nephropathy is one of the major complications of Fabry disease and mainly includes reduced glomerular filtration rate and proteinuria. Affected patients show different degrees of annual loss of renal function according to the magnitude of proteinuria and decrease in estimated glomerular filtration rate (eGFR) at the baseline. Objetive: To analyze the relationship between age at diagnosis and severity of nephropathy in a Fabry disease population. Methods: Cross-sectional design with retrospective data collection. Results: Seventy-two patients were studied with mean age of 26.26 ± 16.48 years and 30 men (41.6%). Twenty-seven paediatric patients and 45 adults were included. Thirteen genotypes were found: E398X, L415P, c886A>G, L106R, c.680G>A, A292T, c. 448.delG, R363H, C382Y, R301Q, D109G, del 3 and 4 exons, W81X, all pathogenic mutations of GLA gene. The mean eGFR in paediatric population was 115.81 ± 20.87 ml/min/1.73 m2 and in adults was 80.63 ± 42.22 ml/min/1.73 m2. The Pearson's bilateral correlation coefficient test (value = −0.462) between the age at diagnosis and eGFR indicates inverse correlation between both variables with a strong statistical significance (P = < 0.01). Spearman's bilateral correlation coefficient (value = +0.385) between the variables at diagnosis and the degree of proteinuria indicates direct correlation between both variables with a strong statistical significance (P= <0.01). Conclusions: Diagnosis of Fabry disease patients at a younger age could be a key to improve the nephropathy prognosis and allow early and effective interventions.
Kidney International Reports, 2019
Nefrología (English Edition), 2019
Background: The early detection of Fabry nephropathy is of interest to us. Its treatment is more ... more Background: The early detection of Fabry nephropathy is of interest to us. Its treatment is more effective in early stages. It has been studied by analysing molecular and tissue biomarkers. These have certain disadvantages that hinder its routine use. The aim of this study is to describe the role of the nephrologist in the diagnosis of the disease, and to describe the clinical variables associated with nephropathy in affected patients. Material and methods: Cross-sectional study. Patients were included from three reference centers in Argentina. Results: Seventy two patients were studied (26.26 ± 16.48 years): 30 of which (41.6%) were men and 42 of which (58.4%) were women; 27 pediatric patients and 45 adults. Fourteen "index cases" were detected, 50% of which were diagnosed by nephrologists. Nephropathy was found in 44 patients (61%): 6 pediatric patients and 38 adults. Two types of clinical variables were associated with nephropathy: (i) peripheral nervous system compromise (P ≤ 0.001), angiokeratomas (P ≤ 0.001) and auditory compromise (P = 0.01-0.001), with these being early clinical manifestations of the most severe disease phenotype, and (ii) structural heart disease (P = 0.01-0.001) and central nervous system compromise (P = 0.05-0.01), which are major and late complications, responsible for increased morbidity and mortality and lower life expectancy. Conclusion: The nephrologist plays an important role in the diagnosis of Fabry nephropathy, although the detection thereof owing to its renal involvement would represent a late diagnosis, because nephropathy is associated with late complications of the most severe disease phenotype.
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Papers by norberto antongiovanni