30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case

Abstract

Patients under 5 years were not evaluated in the phase-3 study for enzyme replacement therapy (ERT) in MPS IV A. Here we describe the evolution of a severe Morquio A pediatric patient who was diagnosed at 19 months old and treated by ERT at 21 months old for the next 30 months.Applying the standard ERT protocol on this very young patient appeared to reduce his urinary excretion of glycosaminoglycans (GAGs); the improvements in both the 6 minute-walk test (6MWT) and the stair climb test, however, were no different than those reported in the nature history study. Additionally, this young patient experienced many ERT-associated side effects, and as a result a specific corticosteroid protocol (1 mg/kg of betamethasone the day before and 1 h before the ERT infusion) was given to avoid adverse events. Under these treatments, the height of this patient increased during the first year of the ERT although no more height gain was observed thereafter for 18 months. However, despite of ERT, his bone deformities (including severe pectus carinatum) actually worsened and his medullar cervical spine compression showed no improvement (thus needed decompression surgery).Conclusion: early ERT treatment did not improve the bone outcome in this severe MPS IV A patient after the 30 months-long treatment. A longer term follow up is required to further assess the efficacy of ERT on both the motor and the respiratory function of the patient.

Mucopolysaccharidosis IVA and glycosaminoglycans

“…These pathological findings are consistent with the fact that frequency of need for orthopedic surgical interventions has not been reduced by ERT (average duration of ERT: 2.5 ± 1.0 years) [129]. Early ERT treatment at 21 months old did not improve the bone outcome in a severe MPS IVA patient after the 30 months-long treatment [132]. In the UK, a specific Managed Access Agreement for elosulfase alfa was formulated in December 2015, in which a drug is made available for a limited period of time (e.g.…”

“…The response to ERT is likely to depend on the age of the patient when treatment is initiated and the severity of the clinical condition. It is notable that some patients respond to ERT while others do not respond to ERT although that the mechanism remains unclear [61, 130,132]. The reduction of urine KS seen in treated MPS IVA patients does not predict any improvement in bone pathology and chondrocyte function [131].…”

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

“…Moreover, there are studies showing that ERT for patients with MPS IVA might not always be useful. For example, according to Do Cao et al [27] and Doherty et al [28], early ERT did not improve skeletal outcomes in a patient with severe MPS IVA. Until now, there has been no proof that ERT has an impact on bone lesions.…”

Mucopolysaccharidosis IVA: Diagnosis, Treatment, and Management

“…Currently, this drug is used in the United States, European countries, and other developed countries. Results of clinical trials in a short period showed that elosulfase alfa was well-tolerated and provided improvement of endurance, stabilized forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and left ventricular mass index [85][86][87][88][89][90][91]. While urinary KS level was significantly decreased during receiving ERT, the blood KS level was not changed compared with that in untreated patients [92].…”