Four year follow-up of a case of fucosidosis treated with unrelated donor bone marrow transplantation

Abstract

Summary:Fucosidosis is a rare autosomal recessive lysosomal disorder caused by ␣-fucosidase deficiency. We report a child with fucosidosis, second daughter of non-consanguineous parents, for whom biochemical diagnosis followed clinical evidence of the disease in her older sister. Based on previous experiences, the indication to transplant was considered. Since she lacked a matched sibling, an unrelated marrow donor was found. At prehematopoietic stem cell transplantation evaluation, first signs of neurological involvement were clinically detectable. MRI showed diffuse hypomyelination and auditory brainstem responses and somatic-sensorial evoked potentials were altered. Visual evoked potentials were normal, tortuosity in the retinal veins and peripapillary hemorrhages were detected. Bone marrow transplantation conditioning was with a regimen of busulphan, thiotepa and cyclophosphamide; in vivo Campath 1G, cyclosporin A and short course methotrexate were given to prevent graft-versus-host disease. The patient engrafted rapidly and her post-transplant course was complicated by moderate graft-versus-host disease, transient episodes of idiopathic thrombocytopenic purpura, repeated septic complications and recurrent episodes of Sweet's syndrome. Sequential short tandem repeat polymorphisms on peripheral blood and bone marrow cells documented the persistence of donor engraftment. Follow-up showed a progressive rise of enzymatic levels. Over the last few years, several storage diseases have been treated with hematopoietic stem cell transplantation (HSCT). [3][4][5][6] The enzymatic activity of white blood cells has been proven to rise to normal levels after HSCT. 7 Moreover, the differentiation of donor monocytes into tissue-specific cells such as Kupfer cells, Ito cells, pulmonary or peritoneal macrophages, lymphoid or histiocytic cells of the spleen and lymph nodes or dendritic cells of the skin causes the clearance of the accumulated substrate in many organs. 8 The correction of enzymatic levels has also been demonstrated in the CNS where new microglia and astroglia were shown to originate in the donor's macrophagic system. 9-13 Persistence of engraftment makes it possible to maintain the turnover of these cells and accounts for clinical improvement after HSCT. Intracellular enzyme transfer and uptake of donor-derived enzyme in plasma contribute to improving the advantageous effects of HSCT in these diseases. In the canine model, early HSCT proved to be useful in preventing clinical onset of fucosidosis and in maintaining normal enzymatic levels. 14 Clinical improvement has been reported in human fucosidosis after HSCT. 15,16 In this paper we report on the long-term outcome of fucosidosis in a patient treated with unrelated donor (UD) HSCT. Case reportWe report on the outcome of the second daughter of nonconsanguineous parents, for whom diagnosis followed clinical evidence of the disease in her sister.At the age of 18 months, the patient's older sister underwent cranial MRI which showed a diffuse hypomyelination invo...

Phenotypic spectrum of fucosidosis in Tunisia

“…Fucosidosis has an inexorable progress. Early haematopoietic stem cell transplantation in presymptomatic patients has been carried out and was successful (Miano et al 2001). In Tunisia, however, bone marrow transplantation suffers from the lack of volunteer marrow donor registries and lack of experience of children suffering from lysosomal storage disorders.…”

“…Two types, severe (type I) and milder (type II), can be delineated on the basis of age of onset and grade of severity (George 2001). There is no cure for fucosidosis; however, early bone marrow transplantation (BMT) may present a valid option to cure this otherwise lethal disease (Miano 2001). We present here the clinical presentations and outcomes of 10 Tunisian patients affected with fucosidosis.…”

Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines

“…HCT performed early in the disease course may be beneficial. [74][75][76] Gaucher disease types I, II, III HCT is effective in alleviating most disease manifestations of Gaucher including arresting further neuropsychological deterioration in type III (Norbottnian) disease [77][78][79][80][81] and greatly reducing skeletal problems in severe early onset type I disease. 34,[82][83][84] HCT is not currently regarded as first-line treatment because of the low morbidity of ERT.…”

Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes

“…1 In the past 25 years, nearly a thousand patients with these types of storage disorders, including mucopolysaccharidosis (MPS) type I (Hurler syndrome), other MPS, adrenoleukodystrophy (ALD), metachromatic leukodystrophy (MLD), Krabbe disease, and others have received allogeneic hematopoietic stem cell transplantation (HSCT) with bone marrow from matched or mismatched related donors who were either carriers or noncarriers of the disease, resulting in clinical benefit in many of them. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The benefit is primarily derived from the replacement of missing enzyme produced by donor cells circulating in the blood and also from engraftment of donor-derived glial cells in the brain. [16][17][18][19] However, many children with IMDs who could benefit from HSCT do not have a matched bone marrow donor.…”