Early hematopoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up

Abstract

Mucopolysaccharidosis type II (MPS II - Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans, affecting multiple organs and systems. Enzyme replacement therapy does not cross the blood brain barrier, limiting results in neurological forms of the disease. Another option of treatment for severe MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS type I, since it can preserve neurocognition when performed early in the course of the disease. To date, only few studies have examined the long-term outcomes of HSCT in patients with MPS II. We describe the seven-year follow-up of a prenatally diagnosed MPS II boy with positive family history of severe MPS form, submitted to HSCT with umbilical cord blood cells at 70 days of age. Engraftment after 30 days revealed mixed chimerism with 79% donor cells; after 7 years engraftment remains at 80%. I2S activity 30 days post-transplant was low in plasma and normal in leukocytes and the same pattern is observed to date. At age 7 years growth charts are normal and he is very healthy, although mild signs of dysostosis multiplex are present, as well as hearing loss. The neuropsychological evaluation (Wechsler Intelligence Scale for Children - Fourth Edition - WISC-IV), disclosed an IQ of 47. Despite this low measured IQ, the patient continues to show improvements in cognitive, language and motor skills, being quite functional. We believe that HSCT is a therapeutic option for MPS II patients with the severe phenotype, as it could preserve neurocognition or even halt neurodegeneration, provided strict selection criteria are followed.

Hematopoietic Stem Cell Transplantation for Patients with Mucopolysaccharidosis II

“…Our data show that HSCT is more effective than ERT with improved cognitive outcomes, and if HSCT is performed earlier than at two years of age, cognitive outcomes may be even better. Recently Barth ]et al have reported that a 7-year-old case, who underwent HSCT with umbilical cord blood cells at 70 days of age, showed normal growth in a very healthy condition, improvements in cognitive, language and motor skills, being quite functional although mild signs of dysostosis multiplex and hearing loss [53]. Data from more young HSCT MPS II patients are needed to determine the magnitude of the benefit of early treatment.…”

Oral and craniofacial manifestations in a Hunter syndrome patient with hematopoietic stem cell transplantation: A case report

“…Meanwhile, Barth et al. described the general features of the patient and observed through the magnetic resonance imaging (MRI) evaluation, that the spine was normal and X‐rays showed very mild signs of dysostosis multiplex.…”

“…5,16 We observed stretching of the stylohyoid processes bilaterally and ectopic/retained teeth, while the other oral structures were normal. Meanwhile, Barth et al 8 described the general features of the patient and observed through the magnetic resonance imaging (MRI) evaluation, that the spine was normal and X-rays showed very mild signs of dysostosis multiplex.…”

“…However, there is a possibility of treatment‐related mortality and morbidity from HSCT in MPS patients, and the real neurological benefits are still unclear . The reason for this modality of treatment not being considered as the best option by the medical literature is possibly due to the scarce data available on results and not very good case selection until the present moment . There are still no published data on oral and craniofacial manifestations of a HSCT early treated child with the neuronopathic MPS II phenotype.…”

“…KEY WORDS: mucopolysaccharidosis II , Hunter syndrome , hematopoietic stem cell transplantation , oral manifestations , craniofacial abnormalities Oral manifestations in MPS-II patient with HSCT literature is possibly due to the scarce data available on results and not very good case selection until the present moment. 8 There are still no published data on oral and craniofacial manifestations of a HSCT early treated child with the neuronopathic MPS II phenotype. The aim of this article is to describe the oral and craniofacial findings of a boy diagnosed early with MPS II (4th month of intrauterine life), 7 years after he received HSCT treatment, showing the importance of early diagnosis and HSCT therapy in attenuating the clinical and radiographic oral and craniofacial manifestations.…”