RESUMEN
Antecedentes: la enfermedad de Fabry (Ef) es una enfermedad rara ligada a X secundaria al depósito lisosomal de glicoesfingolípidos, debido a la deficiencia de la enzima alfa galactosidasa A (α-Gal A). A pesar de su baja frecuencia, es una condición que afecta la calidad de vida de los pacientes y disminuye su esperanza de vida. Objetivo: generar recomendaciones informadas para el diagnóstico y tratamiento de pacientes pediátricos (menores de 18 años) con Ef. Material y Métodos: revisión de literatura en bases de datos y literatura gris a partir de 2010, incluyendo guías de práctica clínica, revisiones sistemáticas y estudios primarios. La calidad de evidencia se evaluó de acuerdo con el tipo. Las recomendaciones se sometieron a consenso de expertos a través de metodología Delphi modificada. El acuerdo se definió a partir del 80 %. Resultados: A partir del análisis de la evidencia recolectada se formularon un total de 45 recomendaciones para tamización, diagnóstico y tratamiento de paciente pediátrico con Ef. El panel revisor estuvo conformado por once expertos en el tema. Las recomendaciones fueron aprobadas con puntuaciones entre 82.3 % y 100 %. Conclusiones: las recomendaciones resultantes del consenso de expertos permitirán la toma de decisiones clínicas y estandarización de la práctica en la atención de pacientes pediátricos con Ef en el país y la región. El diagnóstico temprano y oportuno garantiza una disminución del impacto en la calidad de vida de los pacientes y sus familiares
Background: Fabry disease (fD) is a rare X-linked disease characterized by the accumulation of glyco- sphingolipids in lysosomes due to the deficiency in the production of alpha-galactosidase A (α-Gal A) enzyme. Despite its low frequency, this disease has a serious impact on the life expectancy and quality. Objective: To make evidence-based recommendations for the diagnosis and treatment of fD in pediatric patients (<18 years of age). Materials and Methods: A study of databases and gray literature was conducted in 2010, including clinical practice guidelines, systematic reviews, and primary research. The type of evidence was used to determine the quality of evidence. The recommendations were submitted to an expert consensus using the modified Delphi process. The agreement was set at 80%. Conclusions: The recommendations emerging from this expert consensus will enable the standardization of care provision for pediatric patients with fD in Colombia and Latin America and clinical decision-making for disease management. Notably, making an early diagnosis ensures a reduction in the impact of this disease on the quality of life of patients and their families
Fundamento: a doença de Fabry (Df) é uma rara doença ligada ao cromossomo X secundária à deposi- ção lisossômica de glicoesfingolipídeos devido à deficiência da enzima alfa galactosidase A (α-Gal A). Apesar de sua baixa frequência, é uma condição que afeta a qualidade de vida dos pacientes e diminui sua expectativa de vida. Objetivo: gerar recomendações baseadas em evidências para o diagnóstico e tratamento de pacientes pediátricos (com menos de 8 anos de idade) com Df. Materais e Métodos: foi realizada uma revisão da literatura em bases de dados e literatura cinza a partir de 2010, incluindo diretrizes de prática clínica, revisões sistemáticas e estudos primários. A qualidade da evidência foi avaliada de acordo com o tipo de evidência. As recomendações foram submetidas ao consenso de especialistas usando a metodologia Delphi modificada. A concordância foi definida a partir de 80%. Resultados: com base na análise das evidências coletadas, foram formuladas um total de 45 recomendações para triagem, diagnóstico e tratamento de pacientes pediátricos com doença de Fabry. O painel de revisão foi composto por onze especialistas no assunto. As recomendações foram aprovadas com pontuações entre 82,3% e 100%. Conclusões: as recomendações resultantes do consenso de especialistas permitirão a tomada de decisão clínica e a padronização da prática no cuidado de pacientes pediátricos com Df em nível nacional e regional; o diagnóstico precoce e oportuno garante a redução do impacto na qualidade de vida dos pacientes e seus familiares.
Asunto(s)
HumanosRESUMEN
La poliquistosis renal autosómica dominante (PQRAD) se caracteriza por la aparición de quistes renales. Objetivos: Evaluar el crecimiento del volumen renal y de los quistes en los pacientes tratados con sirolimus, en comparación con aquellos que reciben el tratamiento habitual para la PQRAD; evaluar la aparición de efectos adversos relacionados con el uso de sirolimus; evaluar los cambios en la presión arterial, la proteinuria y el filtrado glomerular (FG) estimado. Materiales y métodos: Durante 24 meses se asignaron al azar 12 pacientes con PQRAD a un grupo de tratamiento con sirolimus (6 pacientes recibieron sirolimus 2 a 3 mg/m2/día, con un máximo de 5 mg/día) o a un grupo control (bajo tratamiento habitual). Resultados: De los 12 pacientes, los 6 pertenecientes al grupo de tratamiento con sirolimus tuvieron, al final del estudio, un aumento del volumen renal total y del volumen quístico del 13% y el 32%, respectivamente. En el grupo control, los 6 pacientes restantes tuvieron aumentos del 11% y el 23%, respectivamente. El FG fue normal para ambos grupos. La proteinuria para los grupos de sirolimus y control fue inicialmente 7.3 mg/m2/h y 6 mg/m2/h, respectivamente. Al finalizar el estudio era normal para ambos grupos. Tres pacientes tenían hipertensión arterial, pero a los 24 meses la presión arterial fue normal. Los efectos adversos observados fueron: anemia, diarrea y úlceras bucales. Conclusiones: El sirolimus no disminuyó el volumen renal ni el quístico. No hubo un aumento significativo en la proteinuria o una disminución en el FG. La media de la presión arterial se mantuvo normal.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is characterized by the develop-ment of kidney cysts. Objectives: To assess the growth of kidney and cystic volume in patients treated with rapamycin compared with patients receiving the usual treatment for ADPKD; assess the occurrence of adverse effects associated with the use of sirolimus; evaluate changes in blood pressure, proteinuria and estimated glomerular filtration rate (eGFR). Materials and methods: For a 24-month period, 12 patients with ADPKD were randomly allocated to a sirolimus group (6 patients, received rapamycin, 2-3 mg/m2/day, max. 5 mg/day) and the other 6 patients were allocated to a control group (receiving conventional treatment). Results: Out of the 12 patients, the 6 patients in the sirolimus group had a total increase in kidney and cystic volume of 13% and 32%, respectively, by the end of the study. In the control group, the other 6 patients had increases of 11% and 23%, respectively. eGFR was normal in both groups. Baseline proteinuria was 7.3 mg/m2/hour and 6 mg/m2/hour in the sirolimus- and control groups, respectively. By the end of the study, it was normal in both groups. Three patients had high blood pressure at baseline, but it was normalized at 24 months. Adverse effects were: anemia, diarr-hea, and mouth sores. Conclusions: Sirolimus did not reduce kidney and cystic volume. No significant increase in proteinuria or decrease in eGFR were observed. Mean blood pressure remained normal.
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Riñón Poliquístico Autosómico Dominante/terapia , Riñón/patología , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Espectroscopía de Resonancia Magnética , Insuficiencia Renal Crónica , Tamaño de los ÓrganosRESUMEN
CONTEXT: Two Argentinean siblings (a boy and a girl) from a nonconsanguineous family presented with hypercalcemia, hypercalciuria, hypophosphatemia, low parathyroid hormone (PTH), and nephrocalcinosis. OBJECTIVE: The goal of this study was to identify genetic causes of the clinical findings in the two siblings. DESIGN: Whole exome sequencing was performed to identify disease-causing mutations in the youngest sibling, and a candidate variant was screened in other family members by Sanger sequencing. In vitro experiments were conducted to determine the effects of the mutation that was identified. PATIENTS AND OTHER PARTICIPANTS: Affected siblings (2 y.o. female and 10 y.o male) and their parents were included in the study. Informed consent was obtained for genetic studies. RESULTS: A novel homozygous mutation in the gene encoding the renal sodium-dependent phosphate transporter SLC34A1 was identified in both siblings (c.1484G>A, p.Arg495His). In vitro studies showed that the p.Arg495His mutation resulted in decreased phosphate uptake when compared to wild-type SLC34A1. CONCLUSIONS: The homozygous G>A transition that results in the substitution of histidine for arginine at position 495 of the renal sodium-dependent phosphate transporter, SLC34A1, is involved in disease pathogenesis in these patients. Our report of the second family with two mutated SLC34A1 alleles expands the known phenotype of this rare condition.