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1.
Med. infant ; 29(1): 17-22, Marzo 2022. Tab, ilus
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1366851

ABSTRACT

Objetivo: evaluar la efectividad de la técnica de conteo de grasas y ajuste de enzimas pancreáticas en un grupo de pacientes con insuficiencia pancreática secundaria a fibrosis quística (FQ). Materiales y métodos: En un grupo de pacientes con FQ, sin otra patología asociada, mayores de 1 año, con >10 000 UKD (unidades por kilo por día) de lipasa; se realizó educación y aplicación de técnica de conteo de grasas con ajuste enzimático, solicitando Van de Kamer y registro alimentario de 5 días durante la recolección de la muestra con un intervalo de 3 meses entre ambas determinaciones. Se evaluó la efectividad de la misma y las dosis de enzimas utilizadas mediante el porcentaje de excreción grasa (PEG), así como las variaciones en la cantidad de enzimas utilizadas y la ganancia de peso. Los datos se registraron en RED Cap (Research Electronic Data Capture) y se analizaron mediante Stata 12. Resultados: De un total de 21 pacientes, 16 completaron la intervención. El 50% presentó un índice de masa corporal (IMC) mayor del Plo 25 antes y después, un 87% alcanzó adecuación calórica mayor del 120% de la ingestas diarias recomendadas (RDA) al final, logrando un aumento promedio de z score de peso de 0,28 con una media inicial de 17 kg y final de 18,2 kg. En cuanto a la media del requerimiento enzimático fue de 14 800 UKD antes y 10 145 UKD después (z=0,002), asimismo el porcentaje de excreción grasa (PEG) tuvo una disminución del 38% (p=0,1705). Conclusiones: La implementación de la técnica de conteo de grasas y ajuste enzimático, podría ser una estrategia válida para aquellos pacientes con FQ que tienen dosis altas de enzimas e inadecuada ganancia de peso (AU)


Objective: To evaluate the effectiveness of the fat counting technique and pancreatic enzyme adjustment in a group of patients with pancreatic insufficiency secondary to cystic fibrosis (CF). Materials and methods: A group of patients with CF without other associated diseases, older than 1 year of age, lipase dose >10 000 UKD (units per kilo per day), received education on the fat counting technique with enzyme adjustment followed by its implementation of the intervention. Van de Kamer was requested and a 5-day food record was kept during the sample collection with an interval of 3 months between both measurements. The effectiveness of the technique and the enzyme doses used were evaluated based on the percentage of fat excretion (PFE), as well as the variations in the amount of enzymes used and weight gain. Data were recorded in RED Cap (Research Electronic Data Capture) and analyzed using Stata 12. Results: Of a total of 21 patients, 16 completed the intervention. Fifty percent had a body mass index (BMI) greater than Plo 25 before and after the intervention; 87% had achieved a caloric increase greater than 120% of the recommended daily intake (RDA) at the end of the study and an average increase in weight z score of 0.28 with an initial mean of 17 kg and a final mean of 18.2 kg. Mean enzyme requirement was 14 800 UKD before and 10 145 UKD after the intervention (z=0.002). PFE decreased by 38% (p=0.1705). Conclusions: The implementation of the technique of fat counting and enzyme adjustment may be a valid strategy for CF patients with high enzyme doses and inadequate weight gain. (AU)


Subject(s)
Infant , Child, Preschool , Child , Adolescent , Pancreas/enzymology , Exocrine Pancreatic Insufficiency , Dietary Fats/administration & dosage , Cystic Fibrosis/diet therapy , Exocrine Glands/abnormalities , Enzyme Replacement Therapy
3.
Acta neurol. colomb ; 37(3): 127-132, jul.-set. 2021. tab
Article in Spanish | LILACS | ID: biblio-1345051

ABSTRACT

RESUMEN INTRODUCCIÓN: La enfermedad de Fabry (EF) es una enfermedad genética, causada por el déficit de la enzima alfa galactosidasa A (α-Gal A), lo que provoca la acumulación de glicoesfingolípidos en los tejidos. Sus manifestaciones clínicas son variables. Estudios en mujeres heterocigotas reportan la existencia de dolor neuropático como manifestación de neuropatía de fibra pequeña. OBJETIVO: Determinar la presencia de neuropatía de fibra pequeña en mujeres heterocigotas para la EF, mediante la prueba cuantitativa sensorial. MATERIALES Y MÉTODOS: Se evaluaron 33 mujeres heterocigotas para EF y 33 mujeres sanas, con características demográficas similares. A todas se les aplicó la prueba cuantitativa sensorial (Quantitative Sensory Testing por medio de la detección de umbrales de frío (Colà Detection Threshold), calor (Warm Detection Threshold), dolor inducido por calor (Heat-pain Detection Thresholds) y vibración (Vibratory Detection Threshold) en los miembros superior e inferior, utilizando un sistema asistido por computador versión IV (CASE IV, WR Medical Electronics Co., Stillwater, MN). Adicionalmente, al grupo de mujeres heterocigotas para EF, se le evaluó la percepción subjetiva de dolor neuropàtico mediante el cuestionario de síntomas sensitivos neuropáticos positivos (Positive Neuropathic Sensory Symptom). Los resultados de la prueba cuantitativa sensorial se compararon entre los grupos. También se estableció la correlación entre la prueba cuantitativa sensorial y los resultados del cuestionario de síntomas sensitivos neuropáticos positivos. RESULTADOS: Se encontró una diferencia estadísticamente significativa en las pruebas de vibración (p = 0,008), calor (p = 0,017) y dolor inducido por calor (p = 0,04) en el miembro inferior en las mujeres heterocigotas para EF, comparado con el grupo control. Se encontró una correlación inversa estadísticamente significativa entre la intensidad del dolor quemante y el dolor inducido por calor en el miembro inferior (p = 0,018, r = -0,48) y entre la intensidad del dolor al ser rozado o tocado y el dolor inducido por calor en el miembro inferior (p = 0,006, r = -0,49). CONCLUSIÓN: En las mujeres heterocigotas para EF, las pruebas objetivas para establecer la presencia de neuropatía de fibra pequeña son anormales en miembros inferiores y se correlacionan con los síntomas sensitivos.


SUMMARY INTRODUCTION: Fabry disease is a genetic condition caused by alpha-galactosidase A deficiency triggering glycosphingolipid accumulation in tissues. Clinical manifestations are variable. Studies in heterozigous females report the existence of neuropathic pain as manifestation of small fiber neuropathy. OBJECTIVE: To determine presence of small fiber neuropathy in heterozigous females with Fabry disease through Quantitative Sensory Testing (QST). MATERIALS AND METHODS: 33 heterozigous females with fabry disease and 33 healthy females with similar demographic characteristics were evaluated. QST was performed to every female evaluating Cold detection Threshold (CDT), Warm Detection Threshold (WDT), Heat-pain Detection Threshold (HPDT) and Vibratory Detection Threshold (VDT) in upper and lower limbs through Computer Assisted Sensory Examination software (CASE IV, WR Medical Electronics Co., Stillwater, MN). Subjective perception of neuropathic pain was measured through Positive Neuropathic Sensory Symptom questionnaire (P-NSS) in heterozigous females with Fabry disease. QST results were compared between groups. Correlations between QST and P-NSS were established. RESULTS: Statistically significant differences were observed in VDT (p= 0,008), WDT (p= 0,017) and HPDT (p= 0,04) in lower limbs of heterozigous females with Fabry disease compared with control group. Negative correlation was found among burning pain intensity and HPDT at lower limbs (p= 0,018, r= -0,48) and among pain intensity to light touch and HPDT in lower limbs (p= 0,006, r=-0,49). CONCLUSIONS: Objective tests to establish presence of small fiber neuropathy in heterozigous females with Fabry disease are abnormal at lower limbs and correlate with sensory symptoms.


Subject(s)
Sensory Thresholds , Pain Measurement , Fabry Disease , Enzyme Replacement Therapy , Small Fiber Neuropathy , Neuralgia
4.
Medicina (B.Aires) ; 81(2): 173-179, June 2021. graf
Article in English | LILACS | ID: biblio-1287268

ABSTRACT

Abstract Cardiovascular mortality (CVM) has become the major contributor to overall Fabry disease (FD) mortality in the enzyme replacement therapy (ERT) era. Our objectives were to describe causes and potential predictors of mortality in FD adult patients in Argentina, and to assess risk of major adverse cardio vascular events (MACE) in the ERT era. We retrospectively studied 93 consecutive patients treated with alpha-galactosidase A (median follow up: 9.5 years from start of ERT). Mean age at ERT starting was 35±16.3 years. Prevalence of cardiomyopathy and renal disease reached 47% and 41%, respectively. Eleven subjects (11.8%, 95%CI: 5-18%) died during follow up (1.24/100 patient-years). Mean overall survival was 71 years (95%CI: 66-75 years). Seven cases were considered as CVM; main causes were sudden death and stroke. Risk of MACE was 14% (95%CI: 6.9-21.1%; 1.47 events/100 patient-years from start of ERT). All but 2 subjects had at least one comorbid cardiovascular risk factor; however, 86% of patients remained free of MACE during follow-up. CVM remained low and our study was underpowered for detection of predictors of mortality, but it is worth noting that age at diagnosis and ERT starting, left ventricular mass index and renal disease trended to correlate with CVM. Prevalence of hypertension, diabetes and dyslipidemia were lower in FD patients when compared to population level data. As in the Argentinean general population, CVM was the leading cause of mortality among this cohort of consecutive FD patients treated with agalsidase alfa.


Resumen La mortalidad cardiovascular (MCV) se ha convertido en el principal contribuyente a la mortalidad general por enfermedad de Fabry (EF) en la era de la terapia de reemplazo enzimático (TRE). Nuestros objetivos fueron describir las causas y posibles predictores de mortalidad en pacientes adultos con EF en la Argentina, y evaluar el riesgo de eventos cardiovasculares mayores (MACE) en la actual era de TRE. Se estudiaron 93 pacientes consecutivos tratados con agalsidasa-alfa por una mediana de 9.5 años tras iniciar TRE. La edad al inicio de TRE fue 35 ± 16.3 años. La prevalencia de cardiomiopatía y enfermedad renal alcanzó 47% y 41%, respectivamente. Once sujetos (11.8%; IC95%: 5-18%) murieron durante el seguimiento (1.24/100 pacientes/año). La supervivencia global fue 71 años (IC95%: 66-75 años). Siete casos fueron considerados como MCV; las principales causas fueron muerte súbita e ictus. El riesgo de MACE fue 14% (IC95%: 6.9-21.1%; 1.47 eventos/100 pacientes/año desde la ERT). Todos menos 2 sujetos tenían al menos un factor de riesgo cardiovascular, pero el 86% permaneció libre de MACE. Los eventos de MCV fueron escasos. El estudio tuvo reducido poder estadístico para detectar predictores de mortalidad, pero la edad al diagnóstico y al iniciar la TRE, índice de masa ventricular izquierda y enfermedad renal tendieron a correlacionarse con MCV. La prevalencia de hipertensión, diabetes y dislipidemia fue menor en comparación con la población general. Como ocurre con la población general en Argentina, los eventos cardiovasculares fueron la principal causa de muerte en esta cohorte de pacientes consecutivos con EF tratados con agalsidasa-alfa.


Subject(s)
Humans , Adult , Fabry Disease/complications , Fabry Disease/drug therapy , Argentina/epidemiology , Recombinant Proteins/therapeutic use , Retrospective Studies , alpha-Galactosidase/adverse effects , Enzyme Replacement Therapy , Isoenzymes
5.
Arch. argent. pediatr ; 119(1): e41-e44, feb. 2021. tab, ilus
Article in Spanish | LILACS, BINACIS | ID: biblio-1147256

ABSTRACT

La terapia de reemplazo enzimático disminuye la morbilidad y mejora la calidad de vida de los pacientes con mucopolisacaridosisii. Se han descrito reacciones de hipersensibilidad inmediata a este fármaco. La desensibilización es un tratamiento que induce la tolerancia temporaria a una droga y permite al paciente alérgico recibir la medicación.Se presenta el caso de un niño de 7 años con diagnóstico de síndrome de Hunter que, luego de 4 años de tratamiento con idursulfase, tuvo dos episodios de anafilaxia durante la infusión del fármaco. Se detectó inmunoglubulina E específica mediante pruebas cutáneas, y fue positiva la intradermorreacción con dilución 1/10 (0,2 mg/ml). Se realizó un protocolo de desensibilización de 12 pasos, sin presentar eventos adversos. La evaluación alergológica y la posibilidad de desensibilización constituyeron herramientas útiles en el manejo de nuestro paciente


Enzyme replacement therapy with idursulfase decreases morbidity and improves quality of life of patients with mucopolysaccharidosis ii. Immediate hypersensitivity reactions to this drug have been described. Desensitization is a treatment that induces temporary tolerance to a culprit drug, allowing the allergic patient to receive the medication.We present the case of a 7-year-old patient diagnosed with Hunter syndrome who presented, after 4 years of treatment, two episodes of anaphylaxis during the infusion of idursulfase. Detection of specific immunoglobulin E was carried out using skin tests, with intradermal reaction at a 1/10 dilution (0.2 mg/ml) being positive. A 12-step desensitization protocol was performed without presenting adverse events.The allergological evaluation and the possibility of desensitization were useful tools in the management of our patient.


Subject(s)
Humans , Male , Child , Desensitization, Immunologic/methods , Enzyme Replacement Therapy , Mucopolysaccharidosis II/drug therapy , Hypersensitivity, Immediate , Metabolism, Inborn Errors
6.
Article in Portuguese | LILACS | ID: biblio-1359773

ABSTRACT

RESUMO: Objetivos: Apresentar um caso raro de cetoacidose diabética (CAD) e pancreatite secundários ao uso de PEG-asparaginase em paciente pediátrico em tratamento para leucemia linfoblástica aguda (LLA) e alertar quanto aos sinais que remetem a esses diagnósticos. Descrição do caso: Adolescente do sexo feminino, 10 anos e 11 meses, em tratamento para LLA e uso prévio de PEG-asparaginase há seis dias da internação, admitida com choque hipotensivo grave e encaminhada à Unidade de Terapia Intensiva. Inicialmente o quadro foi interpretado como choque séptico. Em seguida a anamnese detalhada e os exames laboratoriais direcionaram para os diagnósticos de CAD e pancreatite, iniciando-se as intervenções específicas. Recebe alta hospitalar após 30 dias, sem necessidade de insulinoterapia, mas com reposição de enzimas pancreáticas. Comentários: Geralmente, às crianças com LLA gravemente enfermos e leucopênicos, atribui-se apenas o diagnóstico de sepse, que é um diagnóstico prioritário. Entretanto, no grupo em uso de PEG-asparaginase, o pediatra emergencista deve estar alerta ao raciocínio diferencial envolvendo CAD e pancreatite, o que pode ser bem difícil inicialmente. O alerta dos diagnósticos diferenciais do choque séptico, mesmo que raros, na assistência a pacientes oncológicos pediátricos, além da correta e pronta identificação do quadro e seu manejo apropriado, correlacionam-se diretamente ao sucesso terapêutico e, em algumas situações, à sobrevivência do paciente. (AU)


ABSTRACT: Objectives: We present a rare case of diabetic ketoacidosis (DKA) and pancreatitis secondary to the use of PEG-asparaginase in a pediatric patient being treated for acute lymphoblastic leukemia (ALL) and draw attention to the signs that refer to these diagnoses. Case description: A female adolescent, aged 10 years and 11 months, undergoing treatment for ALL, used PEG-asparaginase for 6 days prior to admission. She was hospitalized due to severe hypotensive shock and was then referred to the intensive care unit. Initially, the clinical condition was interpreted as septic shock. However, detailed anamnesis and results of laboratory tests led to the diagnoses of DKA and pancreatitis; hence, appropriate interventions were initiated. She was discharged after 30 days without the need for insulin therapy but received pancreatic enzyme replacement therapy. Comments: Generally, diagnosing severely ill and leukopenic children with ALL is only attributed to sepsis, which is a priority diagnosis. However, in the group treated with PEG-asparaginase, the pediatric emergency specialist should consider differential reasoning in patients with DKA and pancreatitis, which can be quite difficult to assess initially. Alertness towards the differential diagnoses of septic shock, although rare, in the care of pediatric oncology patients, in addition to the correct and prompt identification of the condition and provision of appropriate management, directly correlates with treatment success and, in some situations, the improvement in patient's survival. (AU)


Subject(s)
Humans , Female , Child , Pancreatitis , Asparaginase , Diabetic Ketoacidosis , Sepsis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Enzyme Replacement Therapy
7.
Arch. endocrinol. metab. (Online) ; 64(5): 623-629, Sept.-Oct. 2020. tab, graf
Article in English | LILACS | ID: biblio-1131137

ABSTRACT

SUMMARY Hypophosphatasia (HPP) is a rare disease with a high mortality rate in its severe forms. It is caused by mutations within the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme responsible for bone mineralization. In 2015, the Food and Drug Administration approved the use of asfotase alfa, the first medication showing benefit in the treatment of HPP. We describe a case with a 2-year follow-up of the first Brazilian child treated with asfotase alfa. A 5-year-old boy, born to consanguineous parents, was diagnosed with HPP at the age of 20 months. During prenatal ultrasonography, polyhydramnios and shortening of long bones were detected. After birth, he presented delayed motor development, repeated respiratory infections, and bone deformities. At the age of 2 years and 8 months, he started walking and had already lost his primary teeth. He had reduced levels of alkaline phosphatase (ALP), elevated levels of pyridoxal 5'-phosphate (PLP), and a p.Ala33Val (c.98C>T) missense mutation in homozygosis in the TNSALP gene. His parents and sister also had reduced ALP levels, high PLP levels, and the same mutation in heterozygosis. His father and sister were healthy, and his mother was diagnosed with rickets in childhood, which resulted in short physical stature and lower limb deformities. The patient was started on asfotase alfa at the age of 2 years and 10 months. After 2 years of treatment, he improved his motor skills, had no further episodes of severe respiratory infection, and showed improved radiological findings of rickets, without any severe side effect.


Subject(s)
Humans , Male , Infant, Newborn , Child, Preschool , Child , Alkaline Phosphatase , Hypophosphatasia/genetics , Hypophosphatasia/drug therapy , Hypophosphatasia/diagnostic imaging , United States , Recombinant Fusion Proteins , Brazil , Immunoglobulin G , Follow-Up Studies , Enzyme Replacement Therapy
8.
Rev. Hosp. El Cruce ; (26): 28-36, Ago 2020.
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1117090

ABSTRACT

La enfermedad de Fabry es una patología por depósito lisosomal causada por mutaciones en el gen GLA que resulta en la deficiencia de alfa galactosidasa A. Dentro de las complicaciones tardías más comunes se encuentra la insuficiencia renal terminal. Por medio de una revisión bibliográfica en la base PUBMed se busca evidenciar si el trasplante renal representa una opción terapéutica indiscutible para el tratamiento de la nefropatía de Fabry. Hallazgos demuestran la posibilidad de la terapia de reemplazo enzimático que permite proteger al sistema cardiovascular y nervioso del daño progresivo por acumulo lisosomal.


Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene that results in alpha galactosidase A deficiency. One of the most common late complications is end stage renal disease. Through a bibliographic review in the PUBMed database, we seek to demonstrate whether kidney transplantation represents an indisputable therapeutic option for the treatment of Fabry nephropathy. Findings demonstratethepossibility of enzymereplacementtherapythatprotects the cardiovascular and nervoussystemfromprogressivedamagebylysosomalaccumulation.


Subject(s)
Kidney Transplantation , Fabry Disease , Enzyme Replacement Therapy
9.
Medicina (B.Aires) ; 80(5): 487-494, ago. 2020. graf
Article in Spanish | LILACS | ID: biblio-1287201

ABSTRACT

Resumen La enfermedad de Gaucher (EG) es causada por una deficiencia genética de la glucocerebrosidasa (GCasa) que provoca acumulación de glucocerebrósido en hígado, bazo y médula ósea. La terapia temprana de reemplazo enzimático revierte citopenias, visceromegalias y previene lesiones óseas irreversibles, por lo cual el diagnóstico precoz es fundamental. Los algoritmos diagnósticos en uso apuntan a manifestaciones hematológicas clásicas. Los síntomas óseos están presentes en 25-32% de los pacientes pero no suelen despertar sospecha de EG. Diseñamos un programa educativo sobre la afectación ósea de la EG y un algoritmo focalizado en la presentación con manifestaciones óseas para facilitar su diagnóstico precoz (proyecto BIG: Bone Involvement in Gaucher Disease). El objetivo del trabajo es describir el proyecto BIG y los resultados de su aplicación en nuestra consulta. Entre marzo de 2017 y diciembre de 2018 se recibieron 38 muestras de sangre seca de pacientes con alguna manifestación ósea sospechosa de EG para cuantificar la actividad de GCasa. Una muestra no cumplía los criterios de inclusión y en 3 de las 37 restantes se observó actividad deficiente de GCasa. El diagnóstico de EG se confirmó por medición de GCasa en leucocitos en dos niñas con manifestaciones óseas de 4 y 2 años de evolución, respectivamente, sin citopenia ni visceromegalia clínicamente evidentes. En el otro paciente con baja actividad la medición en leucocitos fue normal. Los casos detectados muestran la efectividad de un programa educacional de difusión y la utilidad de un algoritmo de detección precoz basado en síntomas óseos que facilitaría el diagnóstico de EG.


Abstract Gaucher disease (GD) is caused by a genetic deficiency of the lysosomal enzyme glucocerebrosidase (GCase) leading to the accumulation of glucocerebroside in the liver, spleen, and bone marrow. The early diagnosis allows a prompt enzyme replacement therapy reversing cytopenias and visceromegaly and preventing irreversible bone lesions. Current diagnostic algorithms are based on well-recognized hematological manifestations. Although bone symptoms are present in 25-32% of the patients, they are not usually suspected as associated with Gaucher disease at clinical presentation. We designed an educational program aimed to give advice on the skeletal involvement in GD and a new diagnostic algorithm that considers bone symptoms to facilitate its early diagnosis (BIG project: Bone Involvement in Gaucher Disease). The study aims at describing the BIG project and the results of its application in our clinic in various cities in Argentina. Within the frame of this project, between March 2017 and December 2018, 38 dry blood spot samples from patients with bone manifestations suspected of having GD were submitted to quantification of GCase activity. One sample did not meet the inclusion criteria. Deficient GCase activity was detected in three of the remaining 37 samples. The diagnosis of GD was confirmed in two girls who presented bone manifestations of 4 and 2 years of evolution, respectively, without hematological alterations. The third patient with low enzyme activity had normal leukocyte GCase. The two newly diagnosed cases of GD show the efficacy of our dual strategy aimed to facilitate the early diagnosis of this rare disease.


Subject(s)
Humans , Female , Gaucher Disease/diagnosis , Glucosylceramidase , Argentina , Early Diagnosis , Enzyme Replacement Therapy
10.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s10-s16, 2020. graf
Article in English | LILACS | ID: biblio-1057106

ABSTRACT

SUMMARY Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The onset of symptoms occurs during childhood, with acroparesthesia, heat intolerance, and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and neuropathic pain. Subsequently, symptoms related to progressive impairment appear, such as angiokeratomas, cornea verticillata, left ventricular hypertrophy, myocardial fibrosis, proteinuria, and renal insufficiency. The latter being the main cause of death in FD. The gold standard for diagnosis is the genetic analysis in search of mutation, in addition to family history. In homozygous patients, the enzyme activity can also be used. Once the diagnosis is confirmed, the patient and their family should receive genetic counseling. The treatment, in turn, currently focuses mainly on replacing the enzyme that is absent or deficient by means of enzyme replacement therapy, with the purpose of avoiding or removing deposits of Gb3. Chaperones can also be used for the treatment of some cases. It is considered that the specific treatment should be initiated as soon as a diagnosis is obtained, which can change the prognosis of the disease.


Subject(s)
Humans , Male , Female , Fabry Disease/pathology , Renal Insufficiency, Chronic/pathology , Enzyme Replacement Therapy , Kidney/pathology , Trihexosylceramides , Fabry Disease/complications , Fabry Disease/genetics , Fabry Disease/therapy , Renal Insufficiency, Chronic/etiology
11.
Ciênc. Saúde Colet ; 24(12): 4717-4726, dez. 2019. tab
Article in Portuguese | LILACS | ID: biblio-1055745

ABSTRACT

Resumo O objetivo deste artigo é avaliar a prevalência e os fatores associados à adesão a terapia de reposição enzimática em adolescentes com Fibrose cística. Estudo transversal, descritivo e observacional. Foram coletados dados sociodemográficos e clínicos. Os instrumentos utilizados para avaliar adesão foram: questionário de Morisky-Green e a dispensação de medicação na farmácia e para os fatores associados, entrevista com questionário estruturado. Foram entrevistados 44 adolescentes. Segundo o método de análise de dispensação da farmácia e o questionário de Morisky-Green, encontramos uma adesão de 45,5% e 11,4%, respectivamente. A maior adesão foi observada naqueles com diagnóstico precoce e a menor nos adolescentes mais velhos e nas meninas. Os fatores com a maior prevalência de não adesão foram: não levar as enzimas ao comer fora de casa, tomar enzimas somente nas grandes refeições, função pulmonar normal, com obstrução grave e muito grave. A prevalência de adesão a enzima foi pequena. Informações relacionadas à doença e ao tratamento devem ser aprimoradas, principalmente em adolescentes mais velhos e com comprometimento da função pulmonar, com criação de estratégias e estudos longitudinais para identificar fatores que interferem na adesão.


Abstract This article sets out to evaluate the prevalence and factors associated with adherence to enzyme replacement therapy among adolescents with cystic fibrosis. It is a cross-sectional, descriptive and observational study. Sociodemographic and clinical data were collected. The instruments used to assess adherence were: the Morisky-Green questionnaire and medication dispensation at the pharmacy, and interviews with structured questionnaires for the associated factors. Forty-four adolescents were interviewed. According to the method of the pharmacy medication dispensation analysis and the Morisky-Green questionnaire, the adherence of 45.5% and 11.4% was found, respectively. The higher adherence was observed in those with early diagnosis and the lowest in older adolescents and girls. The factors with the highest prevalence of non-adherence were: not taking enzymes when eating out of the home; only taking enzymes with major meals; normal lung function; with severe and very severe obstruction. The prevalence of adhesion to enzymes was low. Information related to the disease and treatment should be improved, especially among older adolescents and with impairment of lung function, with the creation of strategies and longitudinal studies to identify factors that interfere with adherence.


Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Cystic Fibrosis/therapy , Medication Adherence/statistics & numerical data , Enzyme Replacement Therapy/statistics & numerical data , Cross-Sectional Studies , Surveys and Questionnaires , Cystic Fibrosis/diagnosis , Early Diagnosis
12.
Rev. Paul. Pediatr. (Ed. Port., Online) ; 37(3): 312-317, July-Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1041342

ABSTRACT

ABSTRACT Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. Results: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event. Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.


RESUMO Objetivo: Descrever a manutenção dos níveis de glicosaminoglicano (GAG) excretados na urina e da estabilização clínica em pacientes com mucopolissacaridose do tipo I (MPS I) com o uso da laronidase num regime de dose alternativo de 1,2 mg/kg a cada duas semanas. Método: Alguns pacientes do nosso serviço participaram de um estudo de otimização de dose da laronidase para o tratamento da MPS I no qual foram comparados quatro esquemas terapêuticos: 0,58 mg/kg/semana, 1,2 mg/kg a cada duas semanas, 1,2 mg/kg/semana e 1,8 mg/kg a cada duas semanas. Após o término do estudo, todos os pacientes passaram a receber a terapia de reposição enzimática (TRE) na dose padrão de bula, que é de 0,58 mg/kg/semana, e nesse regime alguns pais se queixaram da dificuldade em comparecer ao centro todas as semanas, além da dificuldade de se obter acesso para punção venosa. Com base nessas queixas, oito pacientes passaram a receber a TRE no regime alternativo de 1,2 mg/kg a cada duas semanas. Foi feito o estudo retrospectivo de dados de prontuário de pacientes com MPS I que fizeram TRE com laronidase nas doses 0,58 mg/kg/semana e 1,2 mg/kg a cada duas semanas. Resultados: Os pacientes mantiveram-se clinicamente estáveis, não apresentaram aumento dos níveis de GAG urinários nem eventos adversos durante o regime alternativo de dose. Conclusões: A mudança para o esquema de 1,2 mg/kg de laronidase a cada duas semanas foi segura e não acarretou piora clínica nos pacientes que já estavam em TRE na dose padrão.


Subject(s)
Humans , Male , Female , Child , Adolescent , Young Adult , Mucopolysaccharidosis I/drug therapy , Enzyme Replacement Therapy/methods , Iduronidase/therapeutic use , Retrospective Studies , Treatment Outcome , Mucopolysaccharidosis I/physiopathology
13.
J. pediatr. (Rio J.) ; 95(4): 475-481, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1040340

ABSTRACT

Abstract Objective: Mucopolysaccharidosis is a rare genetic disease characterized by the intralysosomal deposition of glycosaminoglycans. Cardiovascular impairment is a common feature. Cardiac signs and symptoms are underestimated due to the disease involvement in other organs. Enzyme replacement therapy can be used in mucopolysaccharidosis I, II, IV, and VI. Thus, the knowledge about the use of new echocardiography tools is relevant to improve the care of this population. This study aimed to describe left ventricular function assessment by conventional echocardiography and left ventricular global longitudinal strain analysis and compare the alterations in patients receiving enzyme replacement therapy and who had different ages at the start of therapy. Method: Outpatient-based descriptive study. The patients were submitted to conventional echocardiography and left ventricular global longitudinal strain measurement. Results: Sixteen patients were evaluated; median age of 14.2 years (SD = 5.2 years). Left ventricular hypertrophy was found in nine patients (56.2%). All patients had preserved left ventricular systolic function (Simpson and Teichholz). Nine (56.2%) patients showed alterations in left ventricular global longitudinal strain. The study showed a positive association between left ventricular hypertrophy and alteration in the left ventricular global longitudinal strain, and late start of enzyme replacement therapy and alteration in the left ventricular global longitudinal strain. Conclusion: Echocardiographic alterations in patients with mucopolysaccharidosis were frequently observed, especially alterations in the left ventricular geometry and subclinical dysfunction. Patients who had a late enzyme replacement therapy start showed an association with worse left ventricular global longitudinal strain values, reinforcing the need for early diagnosis and treatment. The use of new echocardiographic tools may improve the follow-up of these patients.


Resumo Objetivo: A mucopolissacaridose é uma doença genética rara, caracterizada por depósito intralisossômico de glicosaminoglicanos. O comprometimento cardiovascular é frequente. Sinais e sintomas cardíacos são subestimados pelo envolvimento da doença em outros órgãos. A terapia de reposição enzimática pode ser usada em mucopolissacaridose I, II, IV e VI. Assim, o conhecimento da aplicação de novas ferramentas de ecocardiografia é relevante para melhorar a assistência dessa população. Este estudo visou descrever a função do ventrículo esquerdo pelo ecocardiograma convencional e pela análise do strain global longitudinal do ventrículo esquerdo e comparar as alterações em pacientes que fazem uso da terapia de reposição enzimática e que tiveram idades distintas de início da terapia. Método: Estudo descritivo de base ambulatorial. Os pacientes foram submetidos à ecocardiografia convencional e medida do strain global longitudinal do ventrículo esquerdo. Resultados: Foram avaliados 16 pacientes; mediana de 14,2 anos (desvio: 5,2 anos). Hipertrofia do ventrículo esquerdo foi encontrada em nove pacientes (56,2%). Todos os pacientes tiveram função sistólica do ventrículo esquerdo preservada (Simpson e Teichholz). Nove (56,2%) pacientes apresentaram alteração no strain global longitudinal do ventrículo esquerdo. O estudo mostrou associação positiva entre hipertrofia do ventrículo esquerdo e alteração no strain global longitudinal do ventrículo esquerdo e início tardio da terapia de reposição enzimática e alteração no strain global longitudinal do ventrículo esquerdo. Conclusão: Alterações ecocardiográficas em pacientes com mucopolissacaridose foram frequentes, especialmente alterações na geometria e disfunção subclínica do ventrículo esquerdo. Pacientes que iniciaram tardiamente a terapia de reposição enzimática apresentaram associação com piores valores de strain global longitudinal do ventrículo esquerdo, o que reforça a necessidade do diagnóstico e tratamento precoces. O uso de novas ferramentas de ecocardiografia pode melhorar o acompanhamento desses pacientes.


Subject(s)
Humans , Male , Female , Child , Adolescent , Mucopolysaccharidoses/complications , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/diagnostic imaging , Myocardium/pathology , Echocardiography/methods , Cross-Sectional Studies , Mucopolysaccharidoses/drug therapy , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/drug therapy , Enzyme Replacement Therapy
14.
Article | WPRIM | ID: wpr-785411

ABSTRACT

Skeletal mineralization is initiated in matrix vesicles (MVs), the small extracellular vesicles derived from osteoblasts and chondrocytes. Calcium and inorganic phosphate (Pi) taken up by MVs form hydroxyapatite crystals, which propagate on collagen fibrils to mineralize the extracellular matrix. Insufficient calcium or phosphate impairs skeletal mineralization. Because active vitamin D is necessary for intestinal calcium absorption, vitamin D deficiency is a significant cause of rickets/osteomalacia. Chronic hypophosphatemia also results in rickets/osteomalacia. Excessive action of fibroblast growth factor 23 (FGF23), a key regulator of Pi metabolism, leads to renal Pi wasting and impairs vitamin D activation. X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary FGF23-related hypophosphatemia, and enhanced FGF receptor (FGFR) signaling in osteocytes may be involved in the pathogenesis of this disease. Increased extracellular Pi triggers signal transduction via FGFR to regulate gene expression, implying a close relationship between Pi metabolism and FGFR. An anti-FGF23 antibody, burosumab, has recently been developed as a new treatment for XLH. In addition to various forms of rickets/osteomalacia, hypophosphatasia (HPP) is characterized by impaired skeletal mineralization. HPP is caused by inactivating mutations in tissue-nonspecific alkaline phosphatase, an enzyme rich in MVs. The recent development of enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has improved the prognosis, motor function, and quality of life in patients with HPP. This links impaired skeletal mineralization with various conditions, and unraveling its pathogenesis will lead to more precise diagnoses and effective treatments.


Subject(s)
Absorption , Alkaline Phosphatase , Calcium , Chondrocytes , Collagen , Diagnosis , Durapatite , Enzyme Replacement Therapy , Extracellular Matrix , Extracellular Vesicles , Familial Hypophosphatemic Rickets , Fibroblast Growth Factors , Gene Expression , Humans , Hypophosphatasia , Hypophosphatemia , Metabolism , Miners , Osteoblasts , Osteocytes , Prognosis , Quality of Life , Receptors, Fibroblast Growth Factor , Rickets , Signal Transduction , Vitamin D , Vitamin D Deficiency
15.
Article in English | WPRIM | ID: wpr-760211

ABSTRACT

PURPOSE: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. METHODS: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. RESULTS: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. CONCLUSION: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.


Subject(s)
alpha-Glucosidases , Cardiomyopathy, Hypertrophic , Child , Cyanosis , Diagnosis , Electrocardiography , Enzyme Replacement Therapy , Extremities , Female , Follow-Up Studies , Genotype , Glycogen Storage Disease Type II , Hepatomegaly , Humans , Liver , Male , Medical Records , Muscle Hypotonia , Republic of Korea , Retrospective Studies , Seoul , Tachycardia
16.
J. bras. nefrol ; 40(4): 333-338, Out.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-984593

ABSTRACT

ABSTRACT Introduction: Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). Objective: The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). Methods: We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. Results: A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. Conclusion: The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.


RESUMO Introdução: A doença de Fabry (DF) é um distúrbio causado por mutações no gene que codifica a enzima lisossômica α-galactosidase A (α-GAL). A redução da atividade de α-GAL leva ao acúmulo progressivo de globotriaosilceramida (Gb3), também conhecida como CD77. O recente relato de aumento da expressão de CD77 em células sanguíneas de pacientes com DF indicou que essa molécula pode ser utilizada como um potencial marcador para o monitoramento da terapia de reposição enzimática (TRE). Objetivo: O objetivo deste estudo foi avaliar os níveis de CD77 ao longo da TRE em pacientes com DF (mutação V269M). Métodos: Foram avaliadas as flutuações na expressão de CD77 nas membranas das CMSP (células mononucleares do sangue periférico) em pacientes com DF submetidos à TRE e correlacionados com aqueles observados em diferentes tipos de células. Resultados: Uma maior expressão de CD77 foi encontrada em fagócitos de pacientes em comparação aos controles no início do estudo. Curiosamente, a variabilidade nos níveis de CD77 é maior em pacientes no início do estudo (340 - 1619 MIF) e após 12 meses de TRE (240 - 530 MIF) em comparação com o grupo controle (131 - 331 MFI). Além disso, analisando os níveis de CD77 em fagócitos de pacientes ao longo da TRE, encontramos uma diminuição constante nos níveis de CD77. Conclusão: O aumento nos níveis de CD77 nos fagócitos de portadores de Fabry, juntamente com a diminuição nos níveis de CD77 ao longo da TRE, sugerem que medir os níveis de CD77 nos fagócitos é uma ferramenta promissora para monitorar a resposta à TRE na DF.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Trihexosylceramides/biosynthesis , Leukocytes, Mononuclear/metabolism , Fabry Disease/drug therapy , Fabry Disease/blood , alpha-Galactosidase/therapeutic use , Enzyme Replacement Therapy , Trihexosylceramides/analysis , Leukocytes, Mononuclear/chemistry
17.
Rev. méd. Chile ; 146(9): 1079-1084, set. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-978801

ABSTRACT

Fabry's disease is an X-linked multisistemic lisosomal storage disorder caused by deficiency or absence in α-Galatosidase A. Symptoms develop early in childhood with small fiber neuropathy, autonomic disorders and skin lesions (angiokeratomas). More severe in males, patients develop over years heart disease (hypertrophic cardiomyopathy, bradycardia), proteinuria, renal failure, transient ischemic attacks and stroke, associated with decreased life expectancy. We report five patients with Fabry's disease aged between 21 to 56 years and with family history. Neuropathic symptoms are described and neurophysiological testing findings of nerve conduction studies, quantitative sensory testing, autonomic testing and sympathetic skin response are presented.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Fabry Disease/diagnosis , Carbamazepine/therapeutic use , Sensitivity and Specificity , Fabry Disease/drug therapy , Peripheral Nervous System Diseases/diagnosis , Analgesics, Non-Narcotic/therapeutic use , Somatosensory Disorders/diagnosis , Enzyme Replacement Therapy
18.
An. bras. dermatol ; 93(3): 426-428, May-June 2018. graf
Article in English | LILACS | ID: biblio-949873

ABSTRACT

Abstract: Fabry disease is a rare lysosomal storage disorder, inherited in an X-linked manner. It is characterized by the deficiency of the enzyme alpha-galactosidase, leading to a buildup of glycosphingolipids in the cells. Angiokeratoma is one of the cutaneous manifestations of this condition, and it helps making the diagnosis. The typical site involves the genital area in men and lumbosacral, buttocks and trunk region in both sexes. We report a case of genital angiokeratoma in a woman with Fabry disease. The diagnosis is through molecular analysis and, when made early, starting treatment reduces the morbidity and mortality of the disease. Thus, the dermatologist has an important role in the identification of angiokeratoma as a cutaneous marker, and the knowledge of its different presentations is essential for the early diagnosis and management of Fabry disease.


Subject(s)
Humans , Female , Middle Aged , Skin Neoplasms/diagnosis , Vulvar Neoplasms/diagnosis , Fabry Disease/diagnosis , Angiokeratoma/diagnosis , Physician's Role , Skin Neoplasms/pathology , Vulvar Neoplasms/pathology , Diagnosis, Differential , Enzyme Replacement Therapy , Dermatologists , Angiokeratoma/pathology
19.
Rev. chil. obstet. ginecol. (En línea) ; 83(3): 310-317, jun. 2018. tab, graf, ilus
Article in Spanish | LILACS | ID: biblio-959520

ABSTRACT

RESUMEN Introducción y Objetivo: La enfermedad de Gaucher es una condición autosómica recesiva de baja prevalencia, de difícil diagnóstico y manejo, especialmente en embarazo. Reportamos una gestante con enfermedad de Gaucher manejada desde la semana 15,3 hasta el término del embarazo con Taliglucerasa en la Unidad de Alta Complejidad Obstétrica, en la Fundación Valle del Lili en Cali, Colombia. Métodos: Reporte de caso de gestante con diagnóstico de enfermedad de Gaucher diagnosticada durante el embarazo, con exacerbación de síntomas, quien presento severa pancitopenia y esplenomegalia. Resultados: El manejo medico interdiscilplinario permitió el control del severo deterioro clínico de la paciente durante el parto, presentó hemorragia postparto con choque hipovolémico, con adecuada respuesta al manejo médico. La madre y el neonato fueron dados de alta sin otras complicaciones asociadas. Conclusión: El manejo interdisciplinario es indispensable en gestantes con esta entidad para lograr buenos resultados maternos y perinatales.


ABSTRACT Introduction and Objective: Gaucher disease is a low prevalence autosomal recessive condition, difficult to diagnose and manage especially during pregnancy. We reported a pregnant woman with Gaucher disease managed with Taliglucerase in a critical care obstetric unit from week 15.3 until the end of her pregnancy, at the Fundación Valle del Lili, Cali, Colombia. Methods: A case report of a pregnant woman diagnosed during her pregnancy with Gaucher disease, who presented severe pancytopenia and splenomegaly. Results: The interdisciplinary medical management allowed the control of the severe clinical deterioration of the patient. During the delivery, she presented postpartum hemorrhage with hypovolemic shock, which resolved with medical management. The mother and the newborn were discharged without other associated complications. Conclusion: Interdisciplinary management is essential for handling a critically ill obstetric patient with Gaucher disease, and to achieve good maternal and perinatal outcomes.


Subject(s)
Humans , Female , Pregnancy , Adult , Young Adult , Thrombocytopenia , Gaucher Disease/diagnosis , Gaucher Disease/etiology , Gaucher Disease/therapy , Pregnancy Complications , Pregnancy Outcome , Treatment Outcome , Colombia , Enzyme Replacement Therapy/methods , Gaucher Disease/complications , Hepatomegaly
20.
Article in Chinese | WPRIM | ID: wpr-690126

ABSTRACT

Pompe disease, also called type II glycogen storage disease, is a rare autosomal recessive inherited disease caused by the storage of glycogen in lysosome due to acid α-glucosidase (GAA) deficiency, with the most severe conditions in the skeletal muscle, the myocardium, and the smooth muscle. Patients may have the manifestations of dyspnea and dyskinesia, with or without hypertrophic cardiomyopathy. GAA gene mutation has ethnic and regional differences, and new mutation sites are found with the advances in research. Gene analysis is the gold standard for the diagnosis of Pompe disease. Conventional methods, such as skin and muscle biopsies and dried blood spot test, have certain limitations for the diagnosis of this disease. In recent years, prenatal diagnosis and newborn screening play an important role in early diagnosis of this disease. Enzyme replacement therapy (ERT) has a satisfactory effect in the treatment of this disease, but it may lead to immune intolerance. New targeted gene therapy and modified ERT will be put into practice in the future. This article reviews the research advances in the diagnosis and treatment of Pompe disease.


Subject(s)
Animals , Enzyme Replacement Therapy , Glycogen Storage Disease Type II , Diagnosis , Genetics , Therapeutics , Humans , Targeted Gene Repair , alpha-Glucosidases , Genetics , Metabolism
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