Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

BackgroundAllogeneic stem cell transplantation is the only curative option for patients with hereditary bone marrow failure syndromes. Umbilical cord blood is an alternative source of stem cells for allogeneic transplantation. Design and MethodsThis multicenter, retrospective study is based on data reported to the Eurocord Registry about patients with hereditary bone marrow failure syndrome who underwent umbilical cord blood transplantation. ResultsSixty-four patients with hereditary bone marrow failure syndromes were transplanted from related (n=20) or unrelated donors (n=44). Diagnoses were Diamond-Blackfan anemia (21 patients), congenital amegakaryocytic thrombocytopenia (16 patients), dyskeratosis congenita (8 patients), Shwachman-Diamond syndrome (2 patients), severe congenital neutropenia (16 patients) and unclassified (1 patient). In the group of patients who received grafts from related donors, all patients but one received an HLA-matched sibling transplant. The median number of total nucleated cells infused was 5¥10 7 /kg. The cumulative incidence of neutrophil recovery at 60 days was 95%. Two patients had grade II-IV acute graft-versus-host disease, while the 2-year cumulative incidence of chronic graft-versus-host disease was 11%. The 3-year overall survival rate was 95%. In the group of patients who received grafts from unrelated donors, 86% had HLA-mismatched grafts and three received two umbilical cord blood units. The median number of total nucleated cells infused was 6.1¥10 7 /kg. The cumulative incidence of neutrophil recovery at day 60 in this group was 55%. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease was 24%, while the 2-year cumulative incidence of chronic graft-versus-host disease was 53%. The 3-year overall survival rate was 61%; better overall survival was associated with age less than 5 years (P=0.01) and 6.1¥10 7 /kg or more total nucleated cells infused (P=0.05). ConclusionsIn patients with hereditary bone marrow failure syndromes, related umbilical cord blood transplantation is associated with excellent outcomes while increasing cell dose and better HLA matching might provide better results in unrelated umbilical cord blood transplantation.Key words: cord blood transplantation, hereditary bone marrow failure syndromes, engraftment, HLA compatibility.Citation: Bizzetto R, Bonfim C, Rocha V, Socié G, Locatelli F, Chan K, Ramirez O, Stein J, Nabhan S, Miranda E, Passweg J, de Souza CA, Gluckman E, on

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-We present the neurological complications evaluated in a series of 1000 patients who underwent hematopoietic stem cell transplantation (hsct). central nervous system (cNs) neurological complications, particularly brain hemorrhages, were the most common, followed by seizures and cNs infections. An unusual neurological complication was Wernicke's encephalopathy. Less frequent neurological complications were metabolic encephalopathy, neuroleptic malignant syndrome, reversible posterior leukoencephalopathy syndrome, brain infarct and movement disorders. the most common neurological complication of the peripheral nervous system was herpes zoster radiculopathy, while peripheral neuropathies, inflammatory myopathy and myotonia were very rarely found.KEY WORDs: neurological complications, hematopoietic stem cell transplantation, stem-cell transplantation. Complicações neurológicas do transplante de células tronco hematopoiéticas (TCTH): estudo retrospectivo em um centro de TCTH no BrasilResumo -Apresentamos as complicações neurológicas avaliadas em uma série de 1000 pacientes submetidos ao transplante de células tronco hematopoiéticas (tcth). As complicações neurológicas do sistema nervoso central foram as mais encontradas, particularmente as hemorragias encefálicas, seguidas por crises convulsivas e por infecções. Uma complicação peculiar foi a encefalopatia de Wernicke. Menos freqüentemente foram encontrados casos de encefalopatia metabólica, síndrome maligna neuroléptica, leucoencefalopatia posterior reversível, infarto cerebral e os distúrbios do movimento. Entre as complicações neurológicas do sistema nervoso periférico a mais encontrada foi a radiculopatia pelo herpes zoster, enquanto que raramente se observaram casos de polineuropatias periféricas, miopatia inflamatória e de miotonia.PALAvRAs-chAvE: complicações neurológicas, transplante de células tronco hematopoiéticas, transplante de precursores hematopoiéticos.

-Bone marrow transplantation (BMT) is a therapeutic option for patients with genetic storage diseases. Between 1979 and 2002, eight patients, four females and four males (1 to 13 years old) were submitted to this pro c e d u re in our center. Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in 2), one had adre n o l e u k o d y s t rophy (ALD) and one had Gaucher disease. Five patients had related and three unrelated BMT donor. Three patients developed graft versus host disease (two MPS I and one MPS VI) and died between 37 and 151 days after transplantation. Five patients survived 4 to 16 years after transplantation. Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient), one patient had no disease progression (ALD) and in one patient this procedure did not change the natural course of the disease (MPS III).KEY WORDS: storage diseases, bone marrow transplantation, genetic neurological diseases, mucopolysaccharidosis, adrenoleukodystrophy, Gaucher disease.Transplante de medula óssea em pacientes com doença de acúmulo: experiência de um país em desenvolvimento RESUMO -O transplante de medula óssea é uma opção terapêutica para os pacientes com doenças de acú-mulo. Entre 1979 e 2002, oito pacientes, quatro femininos e quatro masculinos (entre um e 13 anos de idade) foram submetidos a este procedimento em nosso centro. Seis pacientes apresentavam mucopolissacaridose (MPS I em 3; MPS III em um e MPS VI em 2), um paciente apresentava adre n o l e u c o d i s t rofia e um apresentava doença de Gaucher. Cinco pacientes receberam o transplante de doador aparentado e três de doador não aparentado. Três pacientes desenvolveram doença do enxerto versus hospedeiro (dois com MPS I e um com MPS VI) e faleceram entre 37 e 151 dias após o transplante. Cinco pacientes sobreviveram entre 4 e 16 anos após o transplante. Três tiveram melhora clínica (um MPS I, um MPS VI e o paciente com doença de Gaucher), um paciente não apresentou pro g ressão da doença (adre n o l e u c o d i s t rofi a) e um paciente não teve alteração da história natural da doença (MPS III).