Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Survey on the management of Pompe disease in routine clinical practice in Spain.

BACKGROUND: Despite the availability of several clinical guidelines, not all health professionals use their recommendations to manage patients with Pompe disease, a rare genetic disorder involving high-impact therapy. Through several discussion meetings and a survey, the present study aimed to learn about the management of Pompe disease in routine clinical practice in Spain, to improve clinical care in a real-life situation. RESULTS: The survey was sent to 42 healthcare professionals who manage patients with Pompe disease in their clinical practice. Although most respondents followed the clinical guidelines, clinical practice differed from the expert recommendations in many cases. Approximately 7% did not request a genetic study to confirm the diagnosis before starting treatment, and 21% considered that only two dried blood spot determinations suffice to establish the diagnosis. About 76% requested anti-GAA antibodies when there is a suspicion of lack of treatment efficacy, though a significant percentage of respondents have never requested such antibodies. According to 31% of the respondents, significant impairment of motor function and/or respiratory insufficiency is a requirement for authorizing medication at their hospital. Up to 26% waited for improvements over the clinical follow-up to maintain treatment and withdrew it in the absence of improvement since they did not consider disease stabilization to be a satisfactory outcome. CONCLUSIONS: The results highlight the lack of experience and/or knowledge of some professionals caring for patients with Pompe disease. It is necessary to develop and disseminate simple guidelines that help to apply the expert recommendations better or centralize patient follow-up in highly specialized centers.

Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial.

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Perfil de pacientes con enfermedades minoritarias en Galicia. Perspectiva desde la medicina interna / Clinical profile of patients with rare diseases. An approach from Internal Medicine

Objetivos: Las enfermedades minoritarias constituyen un grupo heterogéneo de patologías de baja prevalencia, con un origen genético en la mayoría de los casos y frecuentemente asociadas a un retraso en su diagnóstico y notable morbi-mortalidad. Conocer las características clínicas y el grado de complejidad asistencial de los pacientes con enfermedades minoritarias que acuden a las consultas de medicina interna en Galicia podría facilitar una atención más eficaz y eficiente. Material y métodos: Estudio epidemiológico, transversal y multicéntrico en pacientes con enfermedad de baja prevalencia ≥ 18 años atendidos en las consultas y unidades específicas de medicina interna en Galicia hasta el 31 de Diciembre de 2020. Se obtuvieron de cada centro el número de pacientes atendidos según la patología, la media en años desde la aparición de los síntomas, número de comorbilidades, número de visitas anuales al centro y a otros especialistas, número de tratamientos (incluidos aquellos de alto impacto económico), grado de deterioro cognitivo y estimación del nivel de dependencia. Resultados: Se analizaron los indicadores de seis centros correspondientes a seis áreas sanitarias de Galicia, representando a un total de 324 pacientes, con una edad media de 41,3 ±15,8 años. Los tres principales grupos de patologías atendidas fueron por este orden las enfermedades genéticas raras, los errores innatos del metabolismo y las enfermedades neurológicas raras. El retraso medio en el diagnóstico fue de 4,8 ±7,9 años y un 34,17% de los pacientes tardaron 5 o más años en tener una confirmación diagnóstica. Este grupo de mayor retraso diagnóstico presenta menor puntuación en la escala de dependencia de Barthel y 1,75 veces mayor utilización de recursos sanitarios (consultas a medicina interna y otras especialidades). El 11,75% de los pacientes presentan un nivel de dependencia severa o total y el 9,9%, un bajo coeficiente intelectual. Conclusiones: ... (AU)

Objectives: Rare diseases (RD) constitute a heterogeneous group of low prevalence conditions, with genetic origin in most cases and frequently associated with a delay in their diagnosis and notable morbidity and mortality. Knowing the clinical profile and the complexity degree of patientswith RD who attend internal medicine units in Galicia could facilitate more effective and efficient care settings. Methods: Epidemiological, cross-sectional and multicenter study in patients with low prevalence diseases ≥ 18 years attending the outpatients departments and specific units of internal medicine in Galicia up to December 31, 2020. Data were collected on the number of patients treatedregarding their condition at each center, the average age at disease onset, number of comorbidities, number of annual visits to the center and other specialists, number of treatments (including those with a high economicimpact), degree of cognitive impairment and assessment of the degree of autonomy. Results: We analyzed data from six participating centers (from six healthareas of Galicia), representing a total of 324 patients, with a mean age of 41.3 ±15.8 years. The three main groups of pathologies treated were, in this order, rare genetic diseases, innate errors of metabolism and rareneurological diseases. The mean delay in diagnosis was 4.8 ±7.9 years and 34.17% of patients took 5 or more years to have a diagnostic confirmation. This group with the longest diagnostic delay has a lower scoreon the Barthel dependency scale and 1.75 times greater use of health resources (consultations with internal medicine and other specialties). 11.75% of the patients present a level of severe or total dependence and 9.9%, a low IQ. Conclusions: Despite their low average age, patients with minority diseases treated in internal medicine services present a high complexity of care derived from the number of comorbidities, visits to consultations, the need for hospital admissions and polypharmacy... (AU)

Enfermedad de Gaucher: una enfermedad multisistémica / Gaucher Disease: a multisystemic disorder

La enfermedad de Gaucher es un trastorno autosómico recesivo raro debido a la ausencia de la enzima glucocerebrosidasa, produciéndose acumulación de glucocerebrósidos en el sistema retículo endotelial. Se manifiesta por hepatoesplenomegalia, alteraciones hemáticas, neurológicas y óseas. Presentamos el caso de una paciente de 19 años de edad que ingresa por dolor abdominal generalizado, cansancio y debilidad, encontrándose hallazgos concordantes con una afectación infiltrativa en vertebras y ambas diáfisis femorales junto con necrosis avascular de ambas cabezas femorales. Se evidenciaron niveles de β glucosidasa disminuidos, y en el estudio genético se encontró la mutación p.Asn409Ser en homocigosis. La terapia de reemplazo enzimático logró normalización de cifras hematológicas al cabo de 6 meses y de tamaño de bazo e hígado al cabo de 1 año. (AU)

Gaucher disease is a rare autosomal recessive disorder due to the absence of the enzyme glucocerebrosidase, causing accumulation of glucocerebrosides in the reticulum endothelial system. It is manifested by hematologic abnormalities, hepatosplenomegaly, and neurological and bone manifestations. We present the case of a 19-year-old patient who was admitted due to generalized abdominal pain, fatigue and weakness, along with infiltrative involvement in vertebrae and both femoral diaphyses together with avascular necrosis of both femoral heads. Decreased levels of β-glucosidase were evidenced, and the genetic study found the p.Asn409Ser mutation in homozygosity. Enzyme replacement therapy achieved normalization of hematological figures after 6 months and of spleen and liver size after 1 year.

Covid 19 and venous thromboembolic disease. Review on a series of patients

No disponible

Resultados preliminares de un programa de cribado del cáncer anal y sus precursores en hombres VIH que tienen sexo con hombres en Vigo-España / Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain

Antecedentes y objetivos: los hombres VIH que tienen sexo con hombres (VIH-HSH) presentan la mayor incidencia de cáncer anal (CA). El estudio tiene como objetivo conocer la prevalencia de la infección anal por virus del papiloma humano de alto riesgo (VPH-AR) y de los hallazgos citológicos e histológicos, así como la implementación de un programa de cribado en el contexto de una ciudad media española, Vigo (España). Método: análisis prospectivo de una cohorte de 264 hombres (VIH-HSH). A los pacientes se les realizó una citología anal y genotipado de VPH-AR para el estudio de la prevalencia de alteraciones citológicas y de la infección VPH-AR. A 209 se les realizó una anoscopia de alta resolución (AAR). Los resultados se relacionaron con variables epidemiológicas, clínicas y analíticas. Resultados: de los 209 pacientes seleccionados, la prevalencia de VPH-AR, alteraciones citológicas e histológicas anales fue de 85,6%, 47,5% y 39,3% respectivamente. La sensibilidad y especificidad para la citología ≥ ASCUS (atipia de células escamosas de significado indeterminado) respecto a las alteraciones histológicas fue de 61% y 85% (OR: 8,7; IC95%: 4,4-17,2), respectivamente. La concordancia observada entre la citología HSIL (lesión escamosa intraepitelial de alto grado) e histología HSIL (AIN-2/3, neoplasia intraepitelial tipo 2 y 3) fue del 64%,(OR: 11,4; IC95%: 3,5-36,7). Un paciente con citología HSIL presentó cáncer escamoso anal prevalente. Conclusiones: la AAR resultó factible y con resultados similares a los de grupos relevantes. Gran prevalencia de la infección anal por VPH-AR y de alteraciones citológicas e histológicas (AU)

Background: Men who have sex with men (MSM) infected with human immunodeficiency virus (HIV) have the highest risk of developing anal cancer (AC). The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV) anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain). Method: Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV)-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA) was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. Results: Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance) cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2), respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL) cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3) histology was 64% (OR: 11.4; IC 95%: 3.6-36.7). One patient with HSIL cytology presented a prevalent anal squamous carcinoma. Conclusions: HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations (AU)

Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain.

BACKGROUND: Men who have sex with men (MSM) infected with human immunodeficiency virus (HIV) have the highest risk of developing anal cancer (AC). The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV) anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain). METHOD: Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV)-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA) was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. RESULTS: Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance) cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2), respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL) cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3) histology was 64% (OR: 11.4; IC 95%: 3.6-36.7). One patient with HSIL cytology presented a prevalent anal squamous carcinoma. CONCLUSIONS: HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations.

[Venous thrombosis associated with central venous catheter use in patients with cancer]. / Trombosis venosa asociada a catéter venoso central en pacientes con cáncer.

The use of central venous catheters for various applications (administration of chemotherapy, blood products and others) in patients with cancer is increasingly frequent. The association between thrombosis and catheter use has been fully established but aspects such as its causes, diagnosis, prophylaxis and treatment have not. We describe a case of thrombosis in a patient with cancer treated with chemotherapy who carried a central venous catheter. We also perform a review of the risk factors, the role of the prophylaxis and the treatment.

Trombosis venosa asociada a catéter venoso central en pacientes con cáncer / Venous thrombosis associated with central venous catheter use in patients with cancer

La utilización de catéteres venosos centrales en pacientes con cáncer para diferentes usos (administración de quimioterapia, productos sanguíneos y otros) es cada vez más frecuente. La asociación de trombosis con catéter está completamente establecida, pero no así aspectos como causas, diagnóstico, profilaxis y tratamiento. Se describe un caso de trombosis en un paciente con cáncer en tratamiento con quimioterapia portador de catéter venoso central y realizamos una revisión de los factores de riesgo, el papel de la profilaxis y el tratamiento (AU)

The use of central venous catheters for various applications (administration of chemotherapy, blood products and others) in patients with cancer is increasingly frequent. The association between thrombosis and catheter use has been fully established but aspects such as its causes, diagnosis, prophylaxis and treatment have not. We describe a case of thrombosis in a patient with cancer treated with chemotherapy who carried a central venous catheter. We also perform a review of the risk factors, the role of the prophylaxis and the treatment (AU)

Comparación de los pacientes de un registro español de enfermedad de Fabry en dos periodos de tiempo / Comparison of patients from a Spanish Registry of Fabry disease in two periods

Background and objective: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, that leads to multiorgan dysfunction and premature death. Data from the first 24 Spanish patients enrolled on the Fabry Outcome Survey (FOS) were published in 2004, with a significant increase in the number of patients since then. This manuscript analyzes whether the clinical profile or diagnosis of these patients between the 2 periods has changed. Patients and methods: In 2009 the FOS included data from 92 patients. Patients included up to 2003 and those included after that year (68) were compared by sex, regarding age at onset of symptoms and diagnosis, severity and previous misdiagnoses. Similar analysis was performed between the index cases (31) and the other patients. Results: Mean delay in diagnosis was 10 years for both sexes. Male had a classic phenotype, and up to 40% of the females reported symptoms. In females, the enzyme activity seemed to determine disease severity. No differences were observed in any parameter when comparing the patients included in the first period to those included afterwards, nor when comparing index cases with the rest of the patients. Conclusions: Registries like FOS have a great value to deepen our understanding of rare diseases. We confirm that women are not just carriers of the disease. There is still a lack of education and awareness in order to include FD in the differential diagnosis of other processes. Complete family studies would allow early diagnosis of this disorder (AU)

Fundamentos y objetivo: La enfermedad de Fabry (EF) es un raro trastorno lisosomal por déficit de la enzima alfa-galactosidasa A, con herencia ligada al cromosoma X, que ocasiona disfunción multiorgánica y muerte temprana. En 2004 se publicaron las características de los primeros 24 pacientes españoles incluidos en el registro Fabry Outcome Survey (FOS), habiendo aumentado significativamente su número desde entonces. Este trabajo analiza si ha habido cambios en el perfil clínico y diagnóstico de los mismos entre los 2 períodos. Pacientes y método: En 2009 existían en el registro FOS datos de 92 pacientes. Se compararon los pacientes de 2003 con los posteriores (68) respecto a la edad de inicio de los síntomas y de diagnóstico, gravedad y diagnósticos previos erróneos, según sexo. Similar análisis se efectuó entre los casos índice (31) y el resto de pacientes. Resultados:En ambos sexos la demora media del diagnóstico fue de 10 años. Los varones presentan un fenotipo clásico, y hasta un 40% de las mujeres referían síntomas. En estas, la actividad enzimática parece condicionar la gravedad de la enfermedad. No hubo diferencias en los parámetros analizados entre los pacientes del primer período y los posteriores, ni al comparar los casos índice con el resto. Conclusiones: Los registros como el FOS poseen valor para ahondar en el conocimiento de las enfermedades minoritarias. Confirmamos que las mujeres no son meras portadoras de la EF. Todavía falta formación y difusión para incluir la EF en el diagnóstico diferencial de otros procesos. Realizar estudios familiares exhaustivos ayudaría a un diagnóstico más precoz (AU)

[Comparison of patients from a Spanish Registry of Fabry disease in two periods]. / Comparación de los pacientes de un registro español de enfermedad de Fabry en dos periodos de tiempo.

BACKGROUND AND OBJECTIVE: Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, that leads to multiorgan dysfunction and premature death. Data from the first 24 Spanish patients enrolled on the Fabry Outcome Survey (FOS) were published in 2004, with a significant increase in the number of patients since then. This manuscript analyzes whether the clinical profile or diagnosis of these patients between the 2 periods has changed. PATIENTS AND METHODS: In 2009 the FOS included data from 92 patients. Patients included up to 2003 and those included after that year (68) were compared by sex, regarding age at onset of symptoms and diagnosis, severity and previous misdiagnoses. Similar analysis was performed between the index cases (31) and the other patients. RESULTS: Mean delay in diagnosis was 10 years for both sexes. Male had a classic phenotype, and up to 40% of the females reported symptoms. In females, the enzyme activity seemed to determine disease severity. No differences were observed in any parameter when comparing the patients included in the first period to those included afterwards, nor when comparing index cases with the rest of the patients. CONCLUSIONS: Registries like FOS have a great value to deepen our understanding of rare diseases. We confirm that women are not just carriers of the disease. There is still a lack of education and awareness in order to include FD in the differential diagnosis of other processes. Complete family studies would allow early diagnosis of this disorder.

Antiphospholipid syndrome mimicking multiple sclerosis in two patients.

Antiphospholipid syndrome can sometimes mimic multiple sclerosis symptoms and, therefore, present difficulties at the time of diagnosis. We describe the cases of two young women with recurrent neurological deficiencies, the presence of antiphospholipid antibodies in serum, and typical demyelinating lesions on magnetic resonance imaging. Initiation of anticoagulant therapy did not result in any new neurological events in either patient.

[Fabry disease in Spain: first analysis of the response to enzyme replacement therapy]. / Enfermedad de Fabry en España: primer análisis de la respuesta al tratamiento de sustitución enzimática.

BACKGROUND AND OBJECTIVE: Fabry disease is a X-linked lysosomal disorder caused by a deficient activity of the enzyme alfa-galactosidase A. Lack of enzyme activity results in progressive accumulation of globotriaosylceramide (Gb3) leading to multiorgan dysfunction and early death. Enzyme replacement therapy (ERT) has recently become available and the database Fabry Outcome Survey (FOS) of Spain gives us the opportunity to asses the efficacy of this therapy. Our objective is to describe the safety and the effects on renal, cardiac and neurological (pain) aspects of ERT with agalsidase alfa. PATIENTS AND METHOD: The effects of 1, 2, 3 and 4 years of ERT with agalsidase alfa on renal function (assessed by estimated glomerular filtration rate), proteinuria, heart size (assessed by echocardiography), arrhythmias, cardiac valvular anomalies and pain (assessed by the need of concomitant pain therapy) were analyzed in 33 patients under treatment. Safety of ERT was assessed by the reported infusion-related reactions in FOS. RESULTS: Overall, treatment with agalsidase alfa stabilized renal function, but the final result depends on the onset of ERT: there is a tendency to stabilization of renal function in those patients with mild deterioration of renal function, a tendency to improve in those patients with moderate deterioration and to worse in those with severe deterioration of renal function. Proteinuria and left ventricular heart size also estabilized under ERT, and pain improved. TSE infusion-related reactions occurred with an incidence of 0.7%. CONCLUSIONS: ERT with agalsidase alfa is safe and stabilized the abnormal clinical parameters observed in patients with Fabry disease.

Enfermedad de Fabry en España: primer análisis de la respuesta al tratamiento de sustitución enzimática / Fabry disease in Spain: first analysis of the response to enzyme replacement therapy

Fundamento y objetivo: La enfermedad de Fabry es un trastorno lisosómico con herencia ligada al cromosoma X debido a una deficiencia de alfagalactosidasa A, lo que produce una acumulación progresiva de globotriaosilceramida (Gb3), que ocasiona disfunción multiorgánica y muerte temprana. Desde hace pocos años disponemos de tratamiento de sustitución enzimática (TSE) y la base de datos Fabry Outcome Survey (FOS) de España brinda la oportunidad de estudiar su efectividad. El objetivo del presente estudio es describir la seguridad del TSE con agalsidasa alfa y su eficacia en el riñón, el corazón y en el dolor. Pacientes y método: Se analizan los efectos a 1, 2, 3 y 4 años del TSE con agalsidasa alfa sobre la función renal (evaluada mediante la estimación de la filtración glomerular), proteinuria, tamaño cardíaco (evaluado mediante ecocardiografía), arritmias, anomalías valvulares cardíacas y dolor (evaluado mediante la necesidad de tratamiento antiálgico concomitante) en 33 pacientes que recibieron TSE. Asimismo se evalúa la seguridad del TSE. Resultados: El tratamiento con agalsidasa alfa estabilizó la función renal, aunque el resultado depende de la situación al inicio del TSE. Existe una tendencia a la estabilización de la función renal en los pacientes con deterioro leve de ésta, una tendencia a la mejoría en aquellos con deterioro moderado y al empeoramiento en aquellos con deterioro grave. La proteinuria y el grosor del ventrículo izquierdo también se estabilizan con TSE y mejora el dolor. Se objetiva una incidencia del 0,7% de reacciones adversas relacionadas con la infusión del tratamiento. Conclusiones: El TSE con agalsidasa alfa es seguro y estabiliza la alteración orgánica objetivada en los pacientes con enfermedad de Fabry

Background and objective: Fabry disease is a X-linked lysosomal disorder caused by a deficient activity of the enzyme alfa-galactosidase A. Lack of enzyme activity results in progressive accumulation of globotriaosylceramide (Gb3) leading to multiorgan dysfunction and early death. Enzyme replacement therapy (ERT) has recently become available and the database Fabry Outcome Survey (FOS) of Spain gives us the opportunity to asses the efficacy of this therapy. Our objective is to describe the safety and the effects on renal, cardiac and neurological (pain) aspects of ERT with agalsidase alfa. Patients and method: The effects of 1, 2, 3 and 4 years of ERT with agalsidase alfa on renal function (assessed by estimated glomerular filtration rate), proteinuria, heart size (assessed by echocardiography), arrhythmias, cardiac valvular anomalies and pain (assessed by the need of concomitant pain therapy) were analyzed in 33 patients under treatment. Safety of ERT was assessed by the reported infusion-related reactions in FOS. Results: Overall, treatment with agalsidase alfa stabilized renal function, but the final result depends on the onset of ERT: there is a tendency to stabilization of renal function in those patients with mild deterioration of renal function, a tendency to improve in those patients with moderate deterioration and to worse in those with severe deterioration of renal function. Proteinuria and left ventricular heart size also estabilized under ERT, and pain improved. TSE infusion-related reactions occurred with an incidence of 0.7%. Conclusions: ERT with agalsidase alfa is safe and stabilized the abnormal clinical parameters observed in patients with Fabry disease