Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study
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...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-020-01618-y |
| _version_ | 1819073654973005824 |
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| author | Can Ficicioglu Dena R. Matalon Nicole Luongo Caitlin Menello Tracy Kornafel Andrew J. Degnan |
| author_facet | Can Ficicioglu Dena R. Matalon Nicole Luongo Caitlin Menello Tracy Kornafel Andrew J. Degnan |
| author_sort | Can Ficicioglu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T17:57:04Z |
| format | Article |
| id | doaj.art-4047ccdb58bb47e39d51151b229030e1 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-21T17:57:04Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-4047ccdb58bb47e39d51151b229030e12022-12-21T18:55:11ZengBMCOrphanet Journal of Rare Diseases1750-11722020-11-0115111010.1186/s13023-020-01618-yDiagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control studyCan Ficicioglu0Dena R. Matalon1Nicole Luongo2Caitlin Menello3Tracy Kornafel4Andrew J. Degnan5Division of Human Genetics/Metabolism, Lysosomal Storage Diseases Program, The Children’s Hospital of Philadelphia, Perelman School of Medicine, The University of PennsylvaniaStanford University, Lucile Packard Children’s HospitalDivision of Human Genetics/Metabolism, Lysosomal Storage Diseases Program, The Children’s Hospital of Philadelphia, Perelman School of Medicine, The University of PennsylvaniaDivision of Human Genetics/Metabolism, Lysosomal Storage Diseases Program, The Children’s Hospital of Philadelphia, Perelman School of Medicine, The University of PennsylvaniaDivision of Human Genetics/Metabolism, Lysosomal Storage Diseases Program, The Children’s Hospital of Philadelphia, Perelman School of Medicine, The University of PennsylvaniaAbington Hospital – Jefferson HealthAbstract 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.https://doi.org/10.1186/s13023-020-01618-yMucopolysaccharidosis IVAEnzyme replacement therapyAnterior beakingPlatyspondylyDiagnosisTreatment |
| spellingShingle | Can Ficicioglu Dena R. Matalon Nicole Luongo Caitlin Menello Tracy Kornafel Andrew J. Degnan Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study Orphanet Journal of Rare Diseases Mucopolysaccharidosis IVA Enzyme replacement therapy Anterior beaking Platyspondyly Diagnosis Treatment |
| title | Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study |
| title_full | Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study |
| title_fullStr | Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study |
| title_full_unstemmed | Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study |
| title_short | Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study |
| title_sort | diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis iva a sibling control study |
| topic | Mucopolysaccharidosis IVA Enzyme replacement therapy Anterior beaking Platyspondyly Diagnosis Treatment |
| url | https://doi.org/10.1186/s13023-020-01618-y |
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