RESUMO
BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A. Central nervous system (CNS) manifestations consist mainly of cerebrovascular events. Brain MRI results are often abnormal. PURPOSE: The aim of the study was to describe CNS involvement in a group of Italian patients with AFD. METHODS: Clinical and brain MRI data of 43 patients with AFD (25 men, 41.94+/-10.83 years old and 18 women, 52.48+/-17.50 years old) were analysed retrospectively. 17 male patients and 7 female patients were under treatment with enzyme replacement therapy (ERT). RESULTS: All 43 patients had signs or symptoms of AFD. 16 men (64%) and 13 women (72%) demonstrated CNS involvement, although with varying severity. Overall, 6 men and 5 women had suffered from cerebrovascular accidents with an age at onset of 33.64+/-13.65 years and 53.68+/-11.71 years, respectively. Brain MR images were abnormal in 16/25 men and in 13/16 women. During CNS monitoring, some patients receiving ERT (5/17 men and 2/6 women) demonstrated neurological deterioration, especially those who had presented with cerebrovascular disease already before starting ERT. CONCLUSIONS: The study demonstrated a high frequency of CNS involvement in homozygous and heterozygous AFD patients, often characterised by early age at onset and abnormal brain MRIs. At present, ERT is widely used; however, potential beneficent effects may be disguised by the progression of irreversible pathology in short-term follow-up. Therefore, primary and secondary prophylaxes of cerebrovascular disease are extremely important.
Assuntos
Encéfalo/patologia , Doença de Fabry/patologia , Imageamento por Ressonância Magnética , Adulto , Idade de Início , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Progressão da Doença , Doença de Fabry/epidemiologia , Doença de Fabry/fisiopatologia , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by lysosomal storage of several glycosphingolipids, affecting virtually all organs and systems. Enzyme replacement therapy (ERT) for AFD has been available since 2001. Due to the highly variable nature of clinical manifestations in patients with AFD, it is very difficult to assess disease progression and the effects of therapy. We used the Mainz Severity Score Index (MSSI) as a measure of disease severity to study the effects of ERT in a population of 30 patients treated with agalsidase alfa for a median of 2.9 years (range, 1.0-6.2 years). Our data show that the MSSI captures the correlation between disease severity and both gender and age (1 - males performing worse than females at baseline and 2 - severity of diseases progresses with age in both sex). Furthermore, after at least 1 year of ERT, total MSSI scores were significantly lower than those at baseline (p < 0.001), suggesting a marked clinical improvement under ERT. In conclusion, the MSSI is a sensitive and useful tool for monitoring disease progression and assessing the effects of ERT in a population of patients from different treatment centres.
Assuntos
Doença de Fabry/tratamento farmacológico , alfa-Galactosidase/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Gerenciamento Clínico , Doença de Fabry/patologia , Feminino , Humanos , Isoenzimas/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do TratamentoRESUMO
The detection of IgG and IgM anti-cytomegalovirus is very important when movements of serum transaminases are noted in absence of positivity for virus of hepatitis in uremic patients on substitutive treatment; in our patients, we have noted a positivity of 67% for the IgG class. Cytomegalic infection must be taken into consideration for the high parenteral transmissibility in addition to the high grade of immunodepression of uremic patients.