Genotypic‐phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey

Abstract

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. ERT caused increased physical endurance and decreased urinary dermatan sulfate/chondroitin sulfate ratios. Changes in growth parameters, cardiac, respiratory, visual, auditory findings, and joint mobility were not significant. All patients and parents reported out an increased quality of life, which were not correlated with clinical results. The most prevalent mutation was p.L321P, accounting for 58.8% of the mutant alleles and two novel mutations (p.G79E and p.E390 K) were found. ERT was a safe but expensive treatment for MPS VI, with mild benefits in severely affected patients. Early treatment with ERT is mandatory before many organs and systems are involved.

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 ).…”

“…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 …”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…Most long-term observational studies confirm a progressive reduction of spleen and liver size with a tendency to normalization [36,38,[40][41][42][43]45,46,[48][49][50][51]59,60,85]. Only some patients are reported with spleen and/or liver size stabilization [42,50,60].…”

“…Cardiopulmonary exercise tests performed on a small group of Morquio A patients enrolled in the MOR-008 study suggested that ERT improves aerobic efficiency, as demonstrated by an increased performance of work at reduced metabolic demand [140]. Some studies showed instead a stabilization or mild decline, less relevant if compared to untreated patients [60,73]. Kenth et al examined, over the course of 10 years, 16 subjects with MPS IVA, 13 of which were on ERT.…”

“…During the study period they saw a general reduction of spirometry values, with a delayed decline in the ERT group and a mild non-significant increase over time of median percent arterial oxygen saturation in patients on ERT [73]. Kiliç et al studied FEV1 and FVC in 4 MPS VI patients before and after starting ERT [60]. Two patients were within normal limits with no changes due to ERT; the other two patients had restrictive and obstructive signs and after ERT one was unchanged and the other worsened [60].…”