Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study
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RESEARCH
Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study Can Ficicioglu1* , Dena R. Matalon2, Nicole Luongo1, Caitlin Menello1, Tracy Kornafel1 and Andrew J. Degnan3
Abstract Background: Mucopolysaccharidosis (MPS) IVA, also known as Morquio A syndrome, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase. Early recognition, diagnosis, and treatment of this progressive, multisystem disease by enzyme replacement therapy (ERT) can lead to improved outcomes and reduced mortality. Methods: This report documents the diagnostic journey and treatment with ERT of three siblings with MPS IVA. Clinical outcome measures included growth, endurance, imaging, cardiac, respiratory, ophthalmology, and laboratory evaluations. Results: Three siblings, diagnosed at 14.7, 10.1, and 3.2 years of age, demonstrated clinical improvement with weekly infusions of 2.0 mg/kg elosulfase alfa ( Vimizim®, BioMarin Pharmaceutical, Novato, CA, USA). Patient 1 (oldest sibling) and Patient 2 (middle sibling) experienced a diagnostic delay of 8 years 7 months and 4 years after symptom onset, respectively. All three patients demonstrated improvements in growth, 6-min walk distance, joint range of motion, and respiratory function after 30 months of ERT. The treatment was well tolerated without any adverse events. Conclusions: This case series highlights the importance of early recognition of the clinical and imaging findings that are initially subtle in MPS IVA. Early treatment with ERT is necessary to slow irreversible disease progression and improve patient outcomes. The oldest sibling experienced improvements in mobility despite severe symptoms resulting from a late diagnosis. When evaluating patients with skeletal anomalies, imaging multiple body regions is recommended. When findings such as anterior beaking of vertebrae or bilateral femoral head dysplasia are present, MPS IVA should be included in the differential diagnosis. Newborn screening must be considered for early detection, accurate diagnosis, and initiation of treatment to reduce morbidity. Keywords: Mucopolysaccharidosis IVA, Enzyme replacement therapy, Anterior beaking, Platyspondyly, Diagnosis, Treatment
*Correspondence: [email protected] 1 Division of Human Genetics/Metabolism, Lysosomal Storage Diseases Program, The Children’s Hospital of Philadelphia, Perelman School of Medicine, The University of Pennsylvania, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA Full list of author information is available at the end of the article
Background Mucopolysaccharidosis (MPS) IVA, also referred to as Morquio A syndrome, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS) [1–4]. Impaired degradation of the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate stemming from reduced GALNS activity results in undegraded GAGs
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