Short Communication Impact of early enzyme-replacement therapy for mucopolysaccharidosis VI: results of a long-term follow-up of Brazilian siblings

Abstract

ABSTRACT. Mucopolysaccharidosis type VI (MPS VI)is an autosomal recessive multisystem lysosomal storage disorder, which is characterized by the deficiency of the enzyme arylsulfatase B encoded by the ARSB gene. Treatment of this disease with enzyme-replacement therapy (ERT) improves the clinical status of and generates hope for MPS VI patients. However, only few reports on patients with MPS VI treated before 5 years of age have been published. Thus, the objective of this study was to compare the clinical parameters of two sisters affected by MPS VI who started ERT at different ages (9 years and 1 year 5 months, respectively) and to determine the most relevant clinical impacts of early treatment after 85 months of evaluation. The treatment was well tolerated by both siblings. ERT in the younger sibling resulted in increased growth, an improved 6-minute walk test, less coarse face, slower progression of cardiac valve disease, and the absence of compressive myelopathy compared to that in her older sister. On the other hand, the older sibling had typical MPS VI phenotypic features before the commencement of ERT. Corneal clouding, clawed hands, and progressive skeletal changes were observed in both siblings despite the treatment. Both siblings displayed reduced frequencies of upper respiratory infections and apnea indices. This study emphasizes that early diagnosis and treatment of MPS VI are critical for a better disease outcome and to enhance the quality of life for these patients.

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings

“…Clinical trials show that ERT can improve quality of life and clinical and physical function, although eventually in the longterm, improvement reaches a plateau [20,21]. Overall, the current literature supports the safety and efficacy of ERT [22], especially when started at a young age [23][24][25][26].…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…Different evolution in the youngest siblings involved development of facial bones, joint stiffness, other skeletal deformities and growth, organomegaly and heart valves [79,80,[145][146][147][148][149]. In two families with MPS VI, joint mobility was preserved in the youngest sibling but progressive bone deformities and corneal clouding had developed also in the youngest sibling [176,177]. All together, these cases underline the importance of early treatment.…”

“…A series of impressive clinical observations in siblings treated at different ages showed that ERT is reasonably able to modify the clinical course of the disease if administered at an early age [142,143,[176][177][178][179][180][181]. These case studies are only observations and not blind placebo-control studies, but they are relevant enough because they all go in the same direction.…”

Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review

“…Table presents a summary on the effect of treatment for each outcome. The studies showed that the enzyme replacement therapy had a positive effect on the patient's survival outcomes (mortality), quality of life specific domains, lung function improvement, increased range of joint motion (joint mobility), physical resistance improvement, reduction of urinary GAG, and growth …”