RESUMO
Children with Hurler syndrome (mucopolysaccharidosis type IH (MPSIH)) have skeletal, joint and soft tissue abnormalities that may persist or progress after hematopoietic stem cell transplantation (HSCT). We report our single center experience with development of carpal tunnel syndrome (CTS) in 43 children with MPSIH after HSCT. Twenty-three children (59%) developed CTS following HSCT; 19 of the 39 children with enzyme activity in the normal or heterozygous range developed CTS (49%), whereas all four children with low heterozygous or absent enzyme activity developed CTS after HSCT. Fourteen of 19 related donor marrow recipients, eight of 19 of those receiving an unrelated donor graft and one of five unrelated cord blood recipients developed CTS. The mean age at surgical release was 4.8 years. With each year increase in age at HSCT, there was a 55% increased risk. Age and enzyme activity after HSCT were significant factors in the development of CTS. Transplantation by 2 years of age reduced the risk of developing CTS by 46%; higher enzyme activity led to a 78% reduction in the risk of developing CTS. However, children transplanted for MPSIH remain at risk for the development of CTS, and should be monitored on an ongoing basis by nerve conduction velocity testing.
Assuntos
Síndrome do Túnel Carpal/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Iduronidase/metabolismo , Mucopolissacaridose I/terapia , Fatores Etários , Síndrome do Túnel Carpal/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Mucopolissacaridose I/enzimologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Globoid cell leukodystrophy is an inherited metabolic disorder of the central nervous system caused by deficiency of the lysosomal enzyme galactocerebrosidase. Haematopoietic stem cell transplantation is the only available effective treatment. The engraftment from normal donors provides competent cells able to correct the metabolic defect. Umbilical cord blood cells have proved to significantly decrease complications and improve engraftment rate compared to adult marrow cells in haematopoietic stem cell transplantation. Umbilical cord blood cells must be of sufficient activity to provide central nervous system recovery after engraftment is obtained. Galactocerebrosidase activity is known to be affected by two polymorphic alleles found at nucleotides 502 and 1637 of the cDNA for this gene. This enzyme activity and the polymorphic alleles noted above were analysed in 83 random samples of umbilical cord blood. The activity, assayed with the fluorogenic substrate 6-hexadecanoylamino-4-methylumbelliferyl-beta-galactopyranoside, in those with neither polymorphic allele was 4.6 +/- 1.7 units (nmol/h per mg protein). This optimal choice of cord blood was found in only 24% of specimens. Homozygotes for 1637T > C with activity of only 1.5 +/- 0.4 units represented 16% of the samples. Those heterozygous for 1637T > C with slightly better activity (2.3 +/- 0.7 units) represented 52% of the samples. Choice of umbilical cord blood for haematopoietic stem cell transplantation, therefore, requires consideration not only of cell quantity and HLA compatibility but also selection for normal alleles to obtain maximal enzymatic activity for central nervous system correction.
Assuntos
Galactosídeos/farmacologia , Galactosilceramidase/sangue , Galactosilceramidase/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Himecromona/análogos & derivados , Leucodistrofia de Células Globoides/sangue , Leucodistrofia de Células Globoides/genética , Leucodistrofia de Células Globoides/terapia , Mutação , Alelos , Sistema Nervoso Central , Criopreservação , DNA Complementar/metabolismo , Sangue Fetal/metabolismo , Antígenos HLA/metabolismo , Heterozigoto , Homozigoto , Humanos , Himecromona/farmacologia , Lisossomos/metabolismo , Polimorfismo GenéticoRESUMO
I-cell disease or mucolipidosis type II, a rare inherited storage disorder of lysosomal enzyme localization, is characterized by dysostosis multiplex, progressive severe psychomotor retardation and death by 5-8 years from congestive heart failure and recurrent pulmonary infections. A 19-month old girl with I-cell disease received a bone marrow transplant (BMT) from an HLA-identical carrier brother. At the age of 7 years, 5 years after BMT, she has no history of respiratory infections. Her cardiac function remains normal with a shortening fraction of 47%, and she continues to gain neurodevelopmental milestones, albeit at a very slow rate. Musculoskeletal deformities have worsened despite BMT. This is the first report describing neurodevelopmental gains and prevention of cardiopulmonary complications in I-cell disease after BMT.
Assuntos
Transplante de Medula Óssea , Mucolipidoses/complicações , Mucolipidoses/terapia , Desenvolvimento Infantil , Cognição , Feminino , Coração/fisiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Lactente , Doenças Musculoesqueléticas/etiologia , Infecções Respiratórias/prevenção & controle , Transplante Homólogo , Resultado do TratamentoRESUMO
Patients with Hurler syndrome (mucopolysaccharidosis type-IH) and metachromatic leukodystrophy (MLD) develop significant skeletal and neurologic defects that limit their survival. Transplantation of allogeneic hematopoietic stem cells results in partial correction of the clinical manifestations. We postulated that some of these defects may be corrected by infusion of allogeneic, multipotential, bone marrow-derived mesenchymal stem cells (MSC). Patients with Hurler syndrome (n = 5) or MLD (n = 6) who previously underwent successful bone marrow transplantation from an HLA-identical sibling were infused with 2-10 x 10(6)/kg MSCs, isolated and expanded from a bone marrow aspirate of the original donor. There was no infusion-related toxicity. In most recipients culture-purified MSCs at 2 days, 30-60 days and 6-24 months after MSC infusion remained of host type. In two patients the bone marrow-derived MSCs contained 0.4 and 2% donor MSCs by FISH 60 days after MSC infusion. In four patients with MLD there were significant improvements in nerve conduction velocities after MSC infusion. The bone mineral density was either maintained or slightly improved in all patients. There was no clinically apparent change in patients' overall health, mental and physical development after MSC infusion. We conclude that donor allogeneic MSC infusion is safe and may be associated with reversal of disease pathophysiology in some tissues. The role of MSCs in the management of Hurler syndrome and MLD should be further evaluated.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucodistrofia Metacromática/terapia , Mesoderma/transplante , Mucopolissacaridose I/terapia , Adolescente , Adulto , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Técnicas de Cultura de Células , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Mesoderma/citologia , Condução Nervosa , Quimeras de Transplante , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
Hurler syndrome (HS) is an autosomal recessive, inherited metabolic storage disorder due to deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. Untreated patients develop progressive mental retardation and multisystem morbidity with a median life expectancy of 5 years. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and even improvement of intellect, with long-term survival. However, children with HS have an increased incidence of graft failure, usually with concomitant autologous marrow reconstitution. Between 1983 and 2000, 71 Hurler children underwent HCT at the University of Minnesota. Of these 71, 19 (27%) experienced graft failure. We report HCT outcomes in all 11 Hurler patients receiving a second HCT at the University of Minnesota. Median age at second HCT was 25 months (range, 16 to 45 months); median time from first HCT was 8 months (range, 4 to 18.5 months). The conditioning regimen consisted of cyclophosphamide/TBI/ATG (n = 8) or busulfan/cyclophosphamide/ATG (n = 3). The source of bone marrow was an unrelated donor in six, matched sibling in four, and mismatched related in one. Five of the 11 grafts were T cell depleted prior to infusion. Overall, 10 of 11 patients showed donor-derived engraftment, of whom three developed grade 3 to 4 acute GVHD. Five of 11 patients are surviving a median of 25 months (range, 2 months to 12 years) with an overall actuarial survival of 50% (95% CI, 27% to 93%) at 4 years. All five show sustained donor engraftment with normalization of IDU activity levels. Three of five evaluable patients demonstrated stabilization of neuropsychological function after second HCT. Currently, allogeneic donor-derived hematopoiesis provides the only chance for long-term survival and improved quality of life in Hurler patients. While graft failure in Hurler patients requires further investigation, a timely second HCT can be well-tolerated and beneficial.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mucopolissacaridose I/cirurgia , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Iduronidase/deficiência , Iduronidase/genética , Iduronidase/metabolismo , Leucócitos/enzimologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Mucopolissacaridose I/enzimologia , Mucopolissacaridose I/psicologia , Testes Neuropsicológicos , Análise de Sobrevida , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
A 20-year-old patient, who received a bone marrow transplant in order to treat metachromatic leukodystrophy (MLD), succumbed to cytomegalovirus (CMV) encephalitis. After CMV viremia developed, the patient received ganciclovir, but he was switched to foscarnet when ganciclovir resistance was suspected. Foscarnet was discontinued because of concern about its potential central nervous system toxicity. Autopsy samples of brain and cerebrospinal fluid contained CMV DNA with a UL97 mutation (M460V) known to confer ganciclovir resistance. No foscarnet resistance mutations were found.
Assuntos
Antivirais/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Encefalite Viral/tratamento farmacológico , Ganciclovir/uso terapêutico , Adulto , Citomegalovirus/genética , Citomegalovirus/imunologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/patologia , Farmacorresistência Viral , Encefalite Viral/etiologia , Encefalite Viral/patologia , Foscarnet/uso terapêutico , Humanos , Leucodistrofia Metacromática/terapia , MasculinoRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the only treatment for selected inherited metabolic storage diseases (IMSD); a significant shortcoming is failure to achieve donor-derived engraftment. This study was undertaken to determine whether busulfan pharmacokinetics (BU PK) are altered in children with IMSD and whether BU concentrations are important in achieving engraftment. BU samples were obtained from 39 IMSD children, including 20 children with Hurler syndrome, undergoing HCT. Patients received oral BU (40 mg/m(2)/dose x 8 doses), cyclophosphamide (60 mg/kg/day x 2 doses) and TBI (750 cGy in one fraction) as a preparative regimen. Median (range) oral clearance corrected for bioavailability (Cl/F in ml/min/kg), area under the curve (AUC in ng min/ml) and BU plasma concentration (Cp in ng/ml) with the fourth dose were 5.2 (2.1-11.4), 318 294 (112 893-640 995) and 950 (314-1780), respectively. Children < 3 years of age had lower AUC and Cp but higher Cl/F (P < or = 0.03). BU Cp (P = 0.06) or marrow cell dose (P = 0.32) was not different in Hurler syndrome compared to other IMSD. A median BU Cp of 959 and 831 ng/ml was achieved in children with full and failed early engraftment, respectively. There was no difference in early and late engraftment between children with Hurler and other IMSD. In conclusion, we found no significant association between engraftment, marrow cell dose and BU exposure when combined with CY and TBI in children with IMSD.
Assuntos
Bussulfano/farmacocinética , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Mucopolissacaridose I/terapia , Administração Oral , Adolescente , Adulto , Área Sob a Curva , Bussulfano/sangue , Bussulfano/toxicidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Lactente , Doenças por Armazenamento dos Lisossomos/complicações , Doenças por Armazenamento dos Lisossomos/terapia , Masculino , Taxa de Depuração Metabólica , Mucopolissacaridose I/complicações , Taxa de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/normas , Transplante Homólogo/métodos , Transplante Homólogo/normas , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidadeRESUMO
BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.
Assuntos
Adrenoleucodistrofia/terapia , Transplante de Medula Óssea , Adrenoleucodistrofia/classificação , Criança , Pré-Escolar , Ácidos Graxos/sangue , Humanos , Inteligência , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.
Assuntos
Transplante de Medula Óssea , Doença de Wolman/terapia , Saúde da Família , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Lactente , Leucócitos/enzimologia , Lipase/metabolismo , Masculino , Mutação , Núcleo Familiar , Doença de Wolman/tratamento farmacológicoRESUMO
BACKGROUND: Odontoid dysplasia is recognized as a major component of the constellation of dysostosis multiplex lesions associated with Hurler's syndrome (MPS 1H). Because of this abnormality, there is an increased risk of atlantoaxial subluxation with potential cervical spinal cord injury. A significant alteration of the natural history of the disease with respect to the visceral, cardiac, and skeletal systems has resulted in an increased life span for MPS 1H patients associated with engraftment from normal donors. OBJECTIVE: The purpose of this study was to evaluate the longitudinal changes of odontoid dysplasia in MPS 1H following engraftment from bone-marrow transplantation (BMT). MATERIALS AND METHODS: A retrospective review of sequential plain film or cervical spine MR was performed in patients with MPS 1H. Odontoid morphology was graded as aplasia, severe dysplasia, moderate dysplasia, mild dysplasia, or normal. Odontoid morphology was plotted against the time interval. Fully engrafted, nontransplanted, and partially engrafted patients had careful imaging evaluation of the odontoid process. RESULTS: Ten patients were studied with a mean interval follow-up of 8.7 years post-BMT. Seven patients were totally engrafted. Two patients were nontransplanted, and one patient had only partial engraftment (20% enzyme activity). All totally engrafted patients had a progressive improvement in the grade of odontoid dysplasia following BMT. Patients with partial engraftment or without transplantation demonstrated static or increasing odontoid dysplasia. MR imaging showed abnormal dural soft-tissue masses at the level of C2 in all patients. Reduction in the grade of odontoid dysplasia was not associated with significant change in the appearance of the upper cervical soft-tissue masses. CONCLUSION: For the first time, this report documents that patients with MPS 1H show a decrease in the degree of odontoid dysplasia on imaging after successful engraftment following BMT.
Assuntos
Doenças do Desenvolvimento Ósseo/patologia , Vértebras Cervicais/patologia , Mucopolissacaridose I/patologia , Doenças da Coluna Vertebral/patologia , Doenças do Desenvolvimento Ósseo/terapia , Transplante de Medula Óssea , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Lactente , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Mucopolissacaridose I/terapia , Radiografia , Estudos Retrospectivos , Doenças da Coluna Vertebral/terapia , Resultado do TratamentoRESUMO
Hunter syndrome is an X-linked metabolic storage disorder arising from deficiency of iduronate sulfatase enzyme activity. Despite the successful use of hematopoietic cell transplantation for a variety of lysosomal and peroxisomal storage diseases, limited benefit occurs following transplantation in either the severe or mild forms of Hunter syndrome. A brief ethical commentary is provided on the case of a boy with mucopolysaccharidosis IIB (ie the mild form) who received an unrelated umbilical cord blood transplant to improve his future quality of life. Bone Marrow Transplantation (2000).
Assuntos
Anemia Hemolítica Autoimune/etiologia , Doenças Autoimunes/etiologia , Ética Médica , Sangue Fetal/citologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucopolissacaridose II/terapia , Bacteriemia/etiologia , Tomada de Decisões , Doença Enxerto-Hospedeiro/etiologia , Humanos , Recém-Nascido , Consentimento Livre e Esclarecido , Masculino , Mucopolissacaridose II/complicações , Qualidade de Vida , Transplante Homólogo/efeitos adversos , Resultado do TratamentoRESUMO
Umbilical cord blood (UCB) has received increasing attention as a source of unrelated hematopoietic stem cells for transplantation. Lysosomal diseases have been effectively treated and normal enzymatic activity has occurred subsequent to engraftment using UCB. The use of donor cells with normal amounts of enzyme, rather than those from carriers whose level may be 50% or less, is an obvious goal. The frequency of such heterozygotes varies from 1:10 to 1:140 or lower depending upon the disease at issue. We assayed the levels of lysosomal enzymes in normal UCB in random samples as well as those used for transplantation. We measured the following enzymatic activities: alpha-l-iduronidase (Hurler), galactocerebrosidase (globoid cell leuko- dystrophy) and arylsulfatase A (metachromatic leukodystrophy). For the latter, levels of activity in UCB are comparable to those found in adult blood. In the case of arylsulfatase B (Maroteaux-Lamy) a level lower than adult level was found. An informed choice by the transplanting physician based on the activity of the relevant enzyme in the UCB donor will provide a better opportunity for an improved prognosis for more complete correction of the recipient's primary disease. Bone Marrow Transplantation (2000) 25, 541-544.
Assuntos
Sangue Fetal/enzimologia , Lisossomos/enzimologia , Adulto , Cerebrosídeo Sulfatase/sangue , Cerebrosídeo Sulfatase/metabolismo , Estudos de Avaliação como Assunto , Galactosilceramidase/sangue , Galactosilceramidase/metabolismo , Humanos , Iduronidase/sangue , Iduronidase/metabolismo , Recém-Nascido , Cinética , Leucócitos/enzimologia , N-Acetilgalactosamina-4-Sulfatase/sangue , N-Acetilgalactosamina-4-Sulfatase/metabolismoRESUMO
Human bone marrow contains mesenchymal stem cells (MSCs) that can differentiate into various cells of mesenchymal origin. We developed an efficient method of isolating and culture expanding a homogenous population of MSCs from bone marrow and determined that MSCs express alpha-L-iduronidase, arylsulfatase-A and B, glucocerebrosidase, and adrenoleukodystrophy protein. These findings raised the possibility that MSCs may be useful in the treatment of storage disorders. To determine if donor derived MSCs are transferred to the recipients with lysosomal or peroxisomal storage diseases by allogeneic hematopoietic stem cell (HSC) transplantation, we investigated bone marrow derived MSCs of 13 patients 1-14 years after allogeneic transplantation. Highly purified MSCs were genotyped either by fluorescence in situ hybridization using probes for X and Y-chromosomes in gender mis-matched recipients or by radiolabeled PCR amplification of polymorphic simple sequence repeats. Phenotype was determined by the measurement of disease specific protein/enzyme activity in purified MSCs. We found that MSCs isolated from recipients of allogeneic HSC transplantation are not of donor genotype and have persistent phenotypic defects despite successful donor type hematopoietic engraftment. Whether culture expanded normal MSCs can be successfully transplanted into patients with storage diseases and provide therapeutic benefit needs to be determined.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças por Armazenamento dos Lisossomos/terapia , Mesoderma/citologia , Transtornos Peroxissômicos/terapia , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , Fenótipo , Polimorfismo Genético , Transplante Homólogo , Resultado do TratamentoRESUMO
Bone marrow transplantation protocols for inherited metabolic storage diseases are unique for each disorder treated. Differences depend also upon how old the patient was when onset occurred and rate of progression of disease. Treatment is directed to prevent or ameliorate the inexorable neurological deterioration that is the major pathophysiological event in all of these inherited metabolic storage diseases.
Assuntos
Adrenoleucodistrofia/terapia , Transplante de Medula Óssea , Leucodistrofia de Células Globoides/terapia , Leucodistrofia Metacromática/terapia , Mucopolissacaridose I/terapia , Adrenoleucodistrofia/fisiopatologia , Humanos , Leucodistrofia de Células Globoides/fisiopatologia , Leucodistrofia Metacromática/fisiopatologia , Mucopolissacaridose I/fisiopatologiaRESUMO
Over 400 patients with lysosomal and peroxisomal storage diseases have received hematopoietic stem cell transplantation from normal donors. Without treatment, all of these diseases have an inexorable fate leading to central nervous system deterioration and early death. On the other hand, all of the engrafted hosts have had a remarkable positive clinical improvement in response to normalization of previously deficient enzymatic activity. Survival data for those engrafted indicates continued life-span as long as two decades beyond transplantation. The particular diseases treated in this way are included in this article. The specific indications and methods for transplantation are also included in this article.
Assuntos
Transplante de Medula Óssea , Doenças do Sistema Nervoso Central/terapia , Erros Inatos do Metabolismo/terapia , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/normas , Doenças do Sistema Nervoso Central/etiologia , Humanos , Erros Inatos do Metabolismo/complicações , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Our purpose was to determine the characteristic MR features of early-onset (before age 2 years) versus late-onset (after age 2 years) globoid cell leukodystrophy (GLD). METHODS: Thirty-four brain MR images in 22 patients with GLD were reviewed. A severity score (0 to 32), based on a point system derived from the location and extent of disease and the presence of focal and/or global atrophy, was calculated for each examination. RESULTS: Of the 22 patients, three were asymptomatic and 19 were symptomatic. Ten patients had early-onset disease, whereas nine had late-onset disease. MR images of all patients showed abnormalities. In the early-onset group (n = 10; mean maximum MR score, 8.1; range, 3-18), 90% had pyramidal tract involvement, 80% had cerebellar white matter involvement, 70% had deep gray matter involvement, 60% had posterior corpus callosal involvement, 50% had parietooccipital white matter involvement, and 40% had cerebral atrophy. Serial MR imaging in four of these patients revealed progressive disease. In the late-onset group (n = 9; mean maximum MR score, 5.6; range, 4-10), 100% had pyramidal tract involvement, 100% had parietooccipital white matter involvement, 89% had posterior corpus callosal involvement, and none had cerebellar white matter involvement, deep gray matter involvement, or cerebral atrophy. Serial MR imaging in one patient with late-onset GLD did not reveal any change. A spectrum of findings was observed in the three patients who were asymptomatic. CONCLUSION: Cerebellar white matter and deep gray matter involvement are present only in early-onset GLD. Pyramidal tract involvement is a characteristic finding in both early- and late-onset GLD. This scoring method for brain MR observations will assist in the objective assessment of the impact of hematopoietic stem cell transplantation in patients with GLD.
Assuntos
Encéfalo/patologia , Leucodistrofia de Células Globoides/diagnóstico , Imageamento por Ressonância Magnética , Adolescente , Idade de Início , Criança , Pré-Escolar , Humanos , LactenteRESUMO
Hematopoietic stem cell transplantation has increased the survival of patients with Hurler syndrome. Genu valgum occurs frequently in untransplanted patients and has been noted in 52% of our patients after stable engraftment. No deformities spontaneously corrected. We describe the orthopaedic management of genu valgum in Hurler syndrome. Medial epiphyseal stapling predictably affects angular deformity in these patients. Recurrence of deformities either after staple dislodgement or surgical removal can occur, and repeated stapling may be required. Surgical epiphyseal stapling has a role in the management of genu valgum in successfully engrafted Hurler patients. We discuss the relationship of this skeletal deformity to other skeletal deformities and alternative therapies for genu valgum.