Treating a teenager with Morquio A syndrome (mucopolysaccharidosis IV A) with Vimizim

The article describes a clinical case of enzyme replacement therapy (ERT) with elosulfase alfa for a teenager with mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome). Treatment was started quite late, at the age of 12, against the background of a severe course of Morquio A syndrome. Nevertheless, the child showedan improvement in enduranceand fine motor skills, and an increase in muscle tone. The article discusses lack of information on modern methods of enzymereplacement therapy, as well as the limitations of this type of therapy. The paper emphasizes the need for an interdisciplinary approach to treat such diseases and alleviate the condition of patients.

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Bisphosphonate Treatment in a Patient Affected by MPS IVA with Osteoporotic Phenotype

Case Reports in Medicine ◽

10.1155/2013/891596 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Albina Tummolo ◽

Orazio Gabrielli ◽

Alberto Gaeta ◽

Maristella Masciopinto ◽

Lucia Zampini ◽

...

Keyword(s):

Therapeutic Option ◽

Keratan Sulfate ◽

Inherited Metabolic Disorder ◽

Allogenic Bone ◽

Enzyme Replacement ◽

Morquio A ◽

Mps Iva ◽

Or Gene ◽

Mucopolysaccharidosis Type Iva ◽

Morquio A Syndrome

Morquio A syndrome (Mucopolysaccharidosis type IVA) (MPS IVA) is a rare inherited metabolic disorder characterized by the defective degradation of keratan sulfate and chondroitin-6-sulfate. Classically, MPS IVA patients present with severe multisystemic involvement and have a short life expectancy. Attenuated forms with clinical features limited to minor skeletal abnormalities and short stature have also been described, sometimes associated to an early-onset osteoporotic phenotype. No treatment with allogenic bone marrow transplantation or gene therapy is currently available for Morquio A syndrome, and enzyme replacement therapy is under evaluation. We report a case of MPS IVA, who manifested tardily attenuated phenotype and significant bone mass reduction, which was treated with a bisphosphonate (BPN), resulting in an improvement of X-ray skeletal aspects and functional bone performance. We suggest that the use of bisphosphonates may be an interesting supportive therapeutic option for Morquio A patients with osteoporotic phenotype, but further studies involving more patients are necessary to confirm our findings.

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A Case Report of a Japanese Boy with Morquio A Syndrome: Effects of Enzyme Replacement Therapy Initiated at the Age of 24 Months

International Journal of Molecular Sciences ◽

10.3390/ijms21030989 ◽

2020 ◽

Vol 21 (3) ◽

pp. 989

Author(s):

Akari Nakamura-Utsunomiya ◽

Toshio Nakamae ◽

Reiko Kagawa ◽

Shuhei Karakawa ◽

Sonoko Sakata ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Body Height ◽

Decompression Surgery ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Morquio A ◽

Mps Iva ◽

Morquio A Syndrome ◽

Elosulfase Alfa

Background: Morquio A syndrome, mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disorder caused by the deficient activity of N-acetylgalactosamine-6-sulfatase (GalNac6S), due to alterations in the GALNS gene. This disorder results in marked abnormalities in bones and connective tissues, and affects multiple organs. Here, we describe the clinical course of a Japanese boy with MPS IVA who began enzyme replacement therapy (ERT) at the age of 24 months. Patient: the patient presented for kyphosis treatment at 22 months of age. An X-ray examination revealed dysostosis multiplex. Uronic acids were elevated in the urine and the keratan sulfate (KS) fraction was predominant. The leukocyte GalNac6S enzyme activity was extremely low. The patient exhibited the c.463G > A (p.Gly155Arg) mutation in GALNS. Based on these findings, his disease was diagnosed as classical (severe) Morquio A syndrome. An elosulfase alfa infusion was initiated at the age of 24 months. The patient’s body height improved from −2.5 standard deviation (SD) to −2 SD and his physical activity increased during the first 9 months on ERT. However, he gradually developed paralysis in the lower legs with declining growth velocity, which required cervical decompression surgery in the second year of the ERT. The mild mitral regurgitation, serous otitis media, and mild hearing loss did not progress during treatment. Conclusion: early initiation of the elosulfase alfa to our patient showed good effects on the visceral system and muscle strength, while its effect on bones appeared limited. Careful observation is necessary to ensure timely surgical intervention for skeletal disorders associated with neurological symptoms. Centralized and multidisciplinary management is essential to improve the prognosis of pediatric patients with MPS IVA.

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Proteomic Analysis in Morquio A Cells Treated with Immobilized Enzymatic Replacement Therapy on Nanostructured Lipid Systems

International Journal of Molecular Sciences ◽

10.3390/ijms20184610 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4610 ◽

Cited By ~ 4

Author(s):

J. Víctor Álvarez ◽

Susana B. Bravo ◽

María García-Vence ◽

María J. De Castro ◽

Asteria Luzardo ◽

...

Keyword(s):

Replacement Therapy ◽

Delivery System ◽

Skeletal Dysplasia ◽

Cellular Protein ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Morquio A ◽

Mps Iva ◽

Mucopolysaccharidosis Type Iva

Morquio A syndrome, or mucopolysaccharidosis type IVA (MPS IVA), is a lysosomal storage disease due to mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. Systemic skeletal dysplasia and the related clinical features of MPS IVA are due to disruption of cartilage and its extracellular matrix, leading to an imbalance of growth. Enzyme replacement therapy (ERT) with recombinant human GALNS, alpha elosulfase, provides a systemic treatment. However, this therapy has a limited impact on skeletal dysplasia because the infused enzyme cannot penetrate cartilage and bone. Therefore, an alternative therapeutic approach to reach the cartilage is an unmet challenge. We have developed a new drug delivery system based on a nanostructure lipid carrier with the capacity to immobilize enzymes used for ERT and to target the lysosomes. This study aimed to assess the effect of the encapsulated enzyme in this new delivery system, using in vitro proteomic technology. We found a greater internalization of the enzyme carried by nanoparticles inside the cells and an improvement of cellular protein routes previously impaired by the disease, compared with conventional ERT. This is the first qualitative and quantitative proteomic assay that demonstrates the advantages of a new delivery system to improve the MPS IVA ERT.

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Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study

Journal of Inherited Metabolic Disease ◽

10.1007/s10545-014-9715-6 ◽

2014 ◽

Vol 37 (6) ◽

pp. 979-990 ◽

Cited By ~ 125

Author(s):

Christian J. Hendriksz ◽

◽

Barbara Burton ◽

Thomas R. Fleming ◽

Paul Harmatz ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Controlled Study ◽

Efficacy And Safety ◽

Phase 3 ◽

Mucopolysaccharidosis Iva ◽

Enzyme Replacement ◽

Morquio A ◽

Morquio A Syndrome ◽

Elosulfase Alfa

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Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01545-y ◽

2020 ◽

Vol 15 (1) ◽

Author(s):

Lina Moisan ◽

David Iannuzzi ◽

Bruno Maranda ◽

Philippe M. Campeau ◽

John J. Mitchell

Keyword(s):

Health Assessment ◽

Respiratory Function Tests ◽

Pathogenic Variant ◽

Classical Form ◽

Enzyme Replacement ◽

Pathogenic Variants ◽

Morquio A ◽

Morquio A Syndrome ◽

Elosulfase Alfa

Abstract Background Morquio A syndrome is a rare, autosomal recessive, progressively debilitating disorder, with multi-system impairments and high medical burden. Quebec, Canada has a large Morquio A population, which is considered unique due to the presence of founder pathogenic variants. The objectives of this study were to document the genetic and clinical heterogeneity of patients with Morquio A in Quebec, to better characterize the phenotype of those with the French Canadian founder pathogenic variant (NM_000512.5: c.1171A>G, p.Met391Val), and to describe the natural history of the patients treated with elosulfase alfa enzyme replacement therapy. Patients with Morquio A were genotyped for pathogenic variants in the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. Clinical data were retrospectively collected from medical charts of patients and included medical history, height, physical examination, respiratory function tests, electrocardiogram, echocardiogram, endurance in the 6-min walk test (6MWT), and activities of daily living (ADL) as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ). Longitudinal data were collected retrospectively and prospectively for patients treated with elosulfase alfa. Results A total of 33 patients, aged 5–63 years, were included in the analysis. Patients with the founder pathogenic variant (n = 17) generally exhibited a non-classical form of Morquio A. As compared with patients with a non-founder pathogenic variant (n = 16), these patients were generally taller, had greater endurance and were better able to perform ADL. However, they still had significant musculoskeletal disease. Most of the 26 patients treated with elosulfase alfa, regardless of pathogenic variant, showed improvements in endurance and ADL. After 5 to 12 months of treatment, the mean improvement from baseline in the 6MWT was 23% and 10 of 14 patients improved in at least one MPS-HAQ domain. Endurance and ADL generally continued to improve or maintained stable in the long term (up to 7 years). Four out of 19 treated patients with echocardiogram data at follow-up showed progression of cardiac disease. Conclusions In Quebec, Canada, Morquio A frequently manifests as a non-classical form of the syndrome due to a founder effect. Patients treated with elosulfase alfa generally show long-term improvement or stability in endurance and function, regardless of pathogenic variant.

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