Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study.

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed. In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients. Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.

Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future.

Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS.

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

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 in Mucopolysaccharidosis Type II: A Literature Review and Critical Analysis

Abstract Mucopolysaccharidosis II (MPS II—Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in iduronate-2 sulfatase. Enzyme replacement therapy does not cross the blood-brain barrier (BBB), limiting the results in neurological forms of the disease. Another treatment option for MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS I since it can preserve neurocognition when performed early in the course of the disease. Even though the intravenous therapy does not cross the BBB, it has become the recommended treatment for MPS II, and HSCT was not often indicated. In an attempt to understand why this treatment modality is rejected by most specialists as a treatment option for patients with Hunter syndrome, we sought to raise all HSCT cases already reported in the scientific literature. Databases used were Medline/PubMed, Lilacs/BVS Cochrane Library, DARE, SciELO, and SCOPUS. Different combinations of the terms "mucopolysaccharidosis II," "Hunter syndrome," "hematopoietic stem cell transplantation," "bone marrow transplantation," and "umbilical cord blood stem cell transplantation" were used. A total of 780 articles were found. After excluding redundant references and articles not related to the theme, 26 articles were included. A descriptive summary of each article is presented, and the main features are summed up. The clinical experience with HSCT in MPS II is small, and most of the available literature is outdated. The available data reveal poor patient selection criteria, varied conditioning regimens, distinct follow-up parameters, and post-HSCT outcomes of interest, making impossible to compare and generalize the results obtained. Recently, after the development of new conditioning protocols and techniques and the creation of bone marrow donor registries and umbilical cord banks, HSCT has become more secure and accessible. It seems now appropriate to reconsider HSCT as a treatment option for the neuronopathic form of MPS II.