Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI: 10-Year follow up

Abstract

Early initiation of enzyme replacement therapy (ERT) has demonstrated clinical benefit in patients with mucopolysaccharidosis type VI (MPS VI), a progressive, multisystem autosomal recessive lysosomal disorder caused by N-acetylgalactosamine-4-sulphatase (ASB) deficiency and the consequent accumulation of glycosaminoglycan. A previous case report highlighted that 3 years of ERT with recombinant human ASB (galsulfase) was well tolerated and effective in two Japanese siblings with MPS VI who initiated ERT at 5.6 years and 6 weeks of age, respectively. This report describes 10-year follow-up data from these two siblings who continued ERT with weekly infusions of galsulfase 1 mg/kg. Ten years of ERT was well tolerated, and the older sibling reached puberty. He had typical MPS VI phenotypic features, but exhibited significant improvement in shoulder range of motion and had largely unchanged hearing and cardiac function. His skeletal deformity remained unchanged. In contrast, in the younger sibling, typical symptoms of MPS VI, including progressive dysmorphic facial features, hepatosplenomegaly, and hearing impairment were largely absent. Her joint mobility was preserved, although skeletal deformity, including claw-hand deformity, was observed. Both siblings had progressive corneal clouding. The observations in these two patients suggest that early ERT initiated in newborns can be well tolerated and effective in preventing or slowing MPS VI disease progression, but is limited in terms of its effects on bone symptoms. For this, new approaches or bone-targeting treatments would be necessary.

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

“…Our study is consistent with the results of other clinical studies, showing acceptable compliance and an acceptable safety profile [23,26,33,34].…”

“…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].…”

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

“…The hearing function and the cognitive development remained stable after treatment . The other outcomes related to cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive results (Table ).…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…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.…”