Developmental outcome in five children with Hurler syndrome after stem cell transplantation: a pilot study

Abstract

Hurler syndrome (mucopolysaccharidosis type 1H; MPS1H) is a lysosomal storage disease caused by a deficiency of α‐L‐iduronidase activity. The natural course of this neurodegenerative disease inevitably leads to premature death within the first 10 years of life. Enzyme replacement therapy is effective in correcting the enzymatic deficiency of organs other than the central nervous system. Hematopoietic stem cell transplantation (SCT) is the only treatment known to prevent psychomotor deterioration. However, the classical transplantation protocols resulted in a high incidence of graft failure and regimen‐related toxicity. Recently, we published a well‐tolerated, fludarabine‐based, radiation‐free conditioning regimen for SCT in patients with Hurler syndrome. Here we report the developmental outcome (assessed by the Denver Developmental Screening Test before and yearly after SCT) of four females and one male with MPS1H (mean age at last follow‐up 71mo, range 42‐87mo) treated in accordance with this strategy. Mean age at SCT was 25 months (range 10‐36mo). All children were engrafted and in ambulatory care. They all showed psychomotor development without neurodegeneration. In all patients, after SCT a regression of intracranial lesions could be seen that paralleled the psychomotor improvements. SCT led to a relative reduction of head circumference in all cases.

Graft failure in the modern era of allogeneic hematopoietic SCT

“…This is in accordance with previously published data, where non-malignant disorders such as metabolic diseases and non-malignant hematological disorders were found to have an increased risk of graft failure. 38,39 Apart from killing of remnant malignant cells, the purpose of the conditioning regimen is mainly to suppress the recipient's immune system and prevent an immunological rejection of the infused donor hematopoietic cells. RIC regimens are; however, used in the elderly as well as in patients with comorbidities, who would probably not be able to tolerate the toxicity associated with myeloablative conditioning regimens.…”

Brain and Spinal MR Imaging Findings in Mucopolysaccharidoses: A Review

“…In relation to HSCT, there have been studies showing a significant improvement of brain MR imaging features with regression of lesions and WMA following successful engraftment. 13,18,42 Those alterations were also accompanied by favorable neurologic outcome. 36 In addition, although it is widely accepted that HSCT has limited or no effect on skeletal manifestations of the disease, current research has shown that odontoid dysplasia can be normalized with the use of this treatment technique.…”

“…18 In relation to their localization, cystic lesions tend to be linear, varying from patchy to diffuse, 12 and affect most brain parts, with periventricular white matter being the most common, followed by the corpus callosum (Fig 5), basal ganglia, subcortical white matter, thalami (Fig 4), and brain stem. 11,12,15,18,20,27,28,37,38,42 In most, dilated PVS range from 2 to 8 mm in diameter, 12,32 though giant cavitary lesions of 1.5 cm in the brain MR imaging of 1 patient with Hurler-Scheie syndrome were also described in the literature. 17 The cystic areas on MR imaging most likely correspond to perivascular expanded fluid spaces, first described as a neuropathologic autopsy sign by Dekaban and Constantopoulos.…”

Evolução motora de paciente com mucopolissacaridose tipo 1

“…Dusing et al demonstraram deficiência nas habilidades motoras globais e finas em crianças com MPS tipo 1, usando a Escala de Bayley (4) e a Escala de Desenvolvimento de Peabody (5) . Em ambos os estudos, mesmo apresentando baixos níveis nessas habilidades, as crianças com MPS tipo 1 mostraram evolução após a intervenção clínica (13) , o que corrobora os achados do caso clínico aqui relatado. A melhora observada na motricidade global pode estar associada ao aprendizado obtido durante a intervenção fisioterapêutica, a qual estimulou o conhecimento de novos movimentos e posturas, permitindo à criança vivenciar e experimentar novos estímulos sensoriais, proprioceptivos, vestibulares e cognitivos.…”