Clinical, biochemical and genetic profiles of patients with mucopolysaccharidosis type IVA (Morquio A syndrome) in Malaysia: the first national natural history cohort study

AbstractMucopolysaccharidosis type IVA (MPSIVA) or Morquio A disease, a lysosomal storage disorder, is caused by N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, resulting in keratan sulfate (KS) and chondroitin-6-sulfate accumulation. Patients develop severe skeletal dysplasia, early cartilage deterioration and life-threatening heart and tracheal complications. There is no cure and enzyme replacement therapy cannot correct skeletal abnormalities. Here, using CRISPR/Cas9 technology, we generate the first MPSIVA rat model recapitulating all skeletal and non-skeletal alterations experienced by patients. Treatment of MPSIVA rats with adeno-associated viral vector serotype 9 encoding Galns (AAV9-Galns) results in widespread transduction of bones, cartilage and peripheral tissues. This led to long-term (1 year) increase of GALNS activity and whole-body correction of KS levels, thus preventing body size reduction and severe alterations of bones, teeth, joints, trachea and heart. This study demonstrates the potential of AAV9-Galns gene therapy to correct the disabling MPSIVA pathology, providing strong rationale for future clinical translation to MPSIVA patients.

Download Full-text

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

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-4-109-117 ◽

2021 ◽

Vol 66 (4) ◽

pp. 109-117

Author(s):

E. E. Gurinova ◽

A. L. Sukhomyasova ◽

A. N. Semyachkina ◽

P. V. Ochirova

Keyword(s):

Muscle Tone ◽

Interdisciplinary Approach ◽

Fine Motor ◽

Enzyme Replacement ◽

Lack Of Information ◽

Morquio A ◽

Mps Iva ◽

Mucopolysaccharidosis Type Iva ◽

Morquio A Syndrome ◽

Elosulfase Alfa

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.

Download Full-text

Vessel shape alterations of the vertebrobasilar arteries in Mucopolysaccharidosis type IVa (Morquio A) patients

European Journal of Radiology ◽

10.1016/j.ejrad.2017.05.026 ◽

2017 ◽

Vol 93 ◽

pp. 128-133 ◽

Cited By ~ 3

Author(s):

Yasemin Tanyildizi ◽

Seyfullah Gökce ◽

Federico Marini ◽

Anna K Mayer ◽

Stefanie Kirschner ◽

...

Keyword(s):

Mucopolysaccharidosis Type ◽

Morquio A ◽

Mucopolysaccharidosis Type Iva

Download Full-text

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.

Download Full-text