Abstract Mucolipidosis II and III (ML II and III) alpha/beta and ML III gamma are lysosomal diseases caused by GlcNAc-1-phosphotransferase deficiency. Previous data indicate that MLII patients have functionally impaired immune system that contributes to predisposition to infections.We evaluated the immunological phenotype of three Brazilian patients with ML III gamma. Our data suggest that the residual activity of GlcNAc-1-phosphotransferase in patients with ML III gamma is enough to allow the targeting of the lysosomal enzymes required for B-cell functions maintenance.

A mucopolissacaridose tipo II (MPS II) é uma doença genética de amplo espectro clínico, caracterizada por deficiência da enzima iduronato-2sulfatase. Revisão sistemática avaliou a eficácia e segurança da terapia de reposição enzimática (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados até 30 de novembro de 2012. Apenas cinco estudos preencheram os critérios de inclusão (ensaios clínicos randomizados - ECRs, ECRs abertos ou séries de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanálise foi realizada para capacidade vital forçada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudanças significativas em ambas as variáveis; também foi encontrado risco aumentado de reações leves relacionadas à infusão e de desenvolvimento de anticorpos IgG à IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS é segura e tem benefício potencial em MPS II, mas estudos adicionais são necessários.

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.

La mucopolisacaridosis tipo II (MPS II) es una enfermedad genética de amplio espectro clínico, caracterizada por una deficiencia de la enzima iduronato-2-sulfatasa. El objetivo fue evaluar la seguridad y eficacia de la Terapia de Reemplazo Enzimático (TRE) con idursulfasa (IDS) en la MPS II. En las bases PubMed/MEDLINE, EMBASE, LILACS y Cochrane Library se inició la búsqueda hasta el 30 de noviembre de 2012. Sólo cinco estudios cumplieron los criterios de inclusión (ensayos controlados aleatorios -ECA, o ECA abiertos o series de casos prospectivo incluyendo > 5 pacientes y evaluación de los resultados pertinentes). El metaanálisis se realizó para la capacidad vital forzada (FVC; absoluta y %) y la distancia caminada en 6 minutos, con cambios significativos en ambas variables; el riesgo también se encuentra aumentado por reacciones leves y anticuerpos IgG, relacionados con la infusión con IDS. El TRE con IDS es seguro y tiene un beneficio potencial en la MPS II, pero se necesitan estudios adicionales.

A mucopolissacaridose tipo II (MPS II) é uma doença genética de amplo espectro clínico, caracterizada por deficiência da enzima iduronato-2sulfatase. Revisão sistemática avaliou a eficácia e segurança da terapia de reposição enzimática (TRE) com idursulfase (IDS) na MPS II. As bases de dados PubMed/MEDLINE, Embase, LILACS e Biblioteca Cochrane foram pesquisados até 30 de novembro de 2012. Apenas cinco estudos preencheram os critérios de inclusão (ensaios clínicos randomizados - ECRs, ECRs abertos ou séries de caso prospectivas, incluindo cinco ou mais pacientes e avaliando desfechos relevantes). Metanálise foi realizada para capacidade vital forçada (CVF; valores absolutos e em %) e para a distância percorrida no teste da caminhada dos seis minutos, com mudanças significativas em ambas as variáveis; também foi encontrado risco aumentado de reações leves relacionadas à infusão e de desenvolvimento de anticorpos IgG à IDS. Em face dos dados apresentados neste estudo, conclui-se que a TRE com IDS é segura e tem benefício potencial em MPS II, mas estudos adicionais são necessários.

Mucopolysaccharidosis type II (MPS II) is a genetic disease of broad clinical spectrum, characterized by a deficiency of the enzyme iduronate2-sulfatase. The aim of this study was to assess whether enzyme replacement therapy (ERT) with idursulfase (IDS) for MPS II is effective and safe. PubMed/MEDLINE, Embase, LILACS, and Cochrane Library were searched until November 30, 2012. Only five articles met the inclusion criteria (randomized controlled trials - RCTs, or open-label trials/prospective case series including > 5 patients and evaluating relevant outcomes). A meta-analysis was performed for forced vital capacity (FVC; absolute and %) and for distance walked on the 6-minute walking test (6MWT). There was a statistically significant increase, but not clinically relevant, in both variables; an increased risk for development of mild infusion-related reactions and IgG antibodies to IDS were also found. The data suggest that ERT with IDS is safe and has a potential benefit for MPS II patients, but further studies are required.

La mucopolisacaridosis tipo II (MPS II) es una enfermedad genética de amplio espectro clínico, caracterizada por una deficiencia de la enzima iduronato-2-sulfatasa. El objetivo fue evaluar la seguridad y eficacia de la Terapia de Reemplazo Enzimático (TRE) con idursulfasa (IDS) en la MPS II. En las bases PubMed/MEDLINE, EMBASE, LILACS y Cochrane Library se inició la búsqueda hasta el 30 de noviembre de 2012. Sólo cinco estudios cumplieron los criterios de inclusión (ensayos controlados aleatorios -ECA, o ECA abiertos o series de casos prospectivo incluyendo > 5 pacientes y evaluación de los resultados pertinentes). El metaanálisis se realizó para la capacidad vital forzada (FVC; absoluta y %) y la distancia caminada en 6 minutos, con cambios significativos en ambas variables; el riesgo también se encuentra aumentado por reacciones leves y anticuerpos IgG, relacionados con la infusión con IDS. El TRE con IDS es seguro y tiene un beneficio potencial en la MPS II, pero se necesitan estudios adicionales.

The specific treatment available for Fabry disease (FD) is enzyme replacement therapy (ERT) with agalsidase alfa or beta. A systematic review and meta-analysis was conducted to assess the efficacy and safety of ERT for FD. Only double-blind, randomized clinical trials (RCTs) comparing agalsidase alfa or beta and placebo were included. ERT with either agalsidase alfa or beta was considered similar for the purposes of analysis. Ten RCTs were identified, which showed improvements in neuropathic pain, in heart abnormalities and in globotriaosylceramide (GL-3) levels. A meta-analysis showed increased odds for fever, rigors, development of IgG antibodies to agalsidase, and no significant association with development of hypertension or reduction in the QRS complex duration on electrocardiogram. The RCTs included in this comparison enrolled few patients, were highly heterogeneous, and were focused mainly on surrogate endpoints, limiting any conclusions as to the real effect of ERT for FD. The available evidence suggests that response to ERT is variable across patient subgroups and that agalsidase may slow progression of FD, with slight improvement of existing changes. Nevertheless, many uncertainties remain, and further studies are necessary.