Safety and Efficacy of Elosulfase Alfa in Australian Patients with Morquio a Syndrome: A Phase 3b Study

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

Enzyme Replacement Therapy With Elosulfase Alfa Decreases Storage of Glycosaminoglycan in White Blood Cells of Patients With Morquio A Syndrome

Abstract Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by a deficient N-acetylgalactosamine-6-sulfate sulfatase activity, leading to cellular storage of undegraded keratan sulfate. Recently enzyme replacement therapy (ERT) was approved for MPS IVA, but some of ERT effects are still unknown. In the present study, we aimed to evaluate the efficacy of elosulfase alfa upon glycosaminoglycan (GAG) storage in peripheral blood white blood cells of patients with MPS IVA treated for 6 months, comparing samples from patients who received weekly infusions of enzyme (ERT-W) versus infusions every other week (ERT-EOW) versus placebo. A significant reduction in GAG storage was observed in both ERT-treated groups, with weekly ERT showing slightly better performance than ERT-EOW.

Clinical, radiologic, and genetic features of Korean patients with Mucopolysaccharidosis IVA / 소아과

PURPOSE: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life. METHODS: MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results. RESULTS: Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively. CONCLUSION: An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

Common N-acetylgalactosamine-6-sulfate sulfatase (GALNS) exon mutations in Brazilian patients with mucopolysaccharidosis IVA (MPS IVA)

Morquio A Syndrome (mucopolysaccharidosis IVA - MPS IVA, OMIM# 253000) is an autosomal recessive inborn error of metabolism caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). We investigated five unrelated Brazilian MPS IVA families for mutations in exons 4, 5, 9 and 10 of the GALNS gene. Six out of the 10 mutant alleles were identified. Taken together with a previous study, which included six unrelated families, common mutations among Brazilian patients were p.N164T, p.G116S and p.G301C. Among one hundred control subjects three novel silent mutations were found (p.A107A; GCC -> GCT, p.Y108Y; TAC -> TAT, p.P357P; CCG -> CCA). Screening starting with exons 4, 5, 9, 10 and 11 may be a good strategy for genotyping of Brazilian patients since these exons include 73 percent of all mutations identified in the current and previous studies.