Kidney function and 24-hour proteinuria in patients with Fabry disease during 36 months of agalsidase alfa enzyme replacement therapy: a Brazilian experience.

BACKGROUND: Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. METHODS: During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/ 1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >or= 90 mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73 m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73 m(2), and stage V as < 15 mL/min/1.73 m(2). RESULTS: Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered. CONCLUSION: Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests that agalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up.

PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.

Satoyoshi syndrome in a Caucasian girl improved with glucocorticoids--a clinical report.

Satoyoshi syndrome (OMIM 600705) is a rare disorder of unknown cause characterized by progressive painful intermittent muscle spasms, amenorrhea, alopecia, malabsorption, and skeletal abnormalities mimicking a skeletal dysplasia. In this report, we describe a Caucasian 12-year-old girl that presented with characteristic manifestations, including alopecia, muscle cramps, and short stature with onset at age 7. Prednisone 60 mg/m(2) every other day and amytriptiline 25 mg QD were administered. After 2 months, alopecia had significantly improved and muscle cramps had almost disappeared, so that glucocorticoid treatment was tapered. Follow-up, 9 months later, showed a normal looking and asymptomatic girl.

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up / Lesões da substância branca na doença de Fabry antes e depois da terapia de reposição enzimática: um seguimento de 2 anos

PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.

OBJETIVO: Relatar os achados neurológicos e de imagem do sistema nervoso central (SNC), observados durante 24 meses de tratamento de reposição enzimática (ERT) com agalsidase-alfa, em pacientes com a doença de Fabry (FD). MÉTODO: 8 pacientes foram incluídos; 6 completaram 24 meses de ERT. Os dados foram obtidos aos 0, 12 e 24 meses de ERT. Lesões de substância branca (WML) foram avaliadas assim como sua relação com a idade e o exame neurológico (escore SNC). RESULTADOS: Os achados de ressonância nuclear magnética foram estáveis em 3 pacientes. As WML e o escore SNC pioraram em um caso; flutuaram em um outro caso; e melhoraram no sexto paciente. No todo, havia 15 WML antes da ERT e 19 WML depois de 24 meses de ERT. Em dois anos, 4 lesões desapareceram e 8 novas surgiram. CONCLUSÕES: Viu-se um padrão difuso de WML assintomáticas, na FD. Em dois anos, algumas WML surgiram, enquanto outras desapareceram. Resta demonstrar se esses fenômenos fazem parte da história natural da doença.

Medicaçäo pré-anestésica / Preanesthetic medication

Os autores fazem uma revisao da literatura, com o objetivo de descrever os fármacos mais utilizados na Medicaçao Pré-anestésica (MPA). Açoes farmacológicas, vantagens e desvantagens da utilizaçao, bem como doses mais indicadas sao analisados visando à adequada prescriçao desses fármacos.

Divertículos do íleo terminal / Terminal ileal diverticula

Resumo: Os autores apresentam um relato de caso a respeito de um paciente de 40 anos de idade que foi internado no Hospital de Clínicas de Porto Alegre para investigaçäo de dor na fossa ilíaca direita. Os exames laboratoriais eram normais. O exame radiológico revelou a presença de divertículos no íleo terminal.