RARE DISEASE
Mucopolysaccharidosis type 6
Mucopolysaccharidosis type 6
Mucopolysaccharidosis type 6
Synonyms: ARSB deficiency, ASB deficiency, Arylsulfatase B deficiency, MPS6, MPSVI, Maroteaux-Lamy disease, Mucopolysaccharidosis type VI, N-acetylgalactosamine 4-sulfatase deficiency
Synonyms: ARSB deficiency, ASB deficiency, Arylsulfatase B deficiency, MPS6, MPSVI, Maroteaux-Lamy disease, Mucopolysaccharidosis type VI, N-acetylgalactosamine 4-sulfatase deficiency
Synonyms: ARSB deficiency, ASB deficiency, Arylsulfatase B deficiency, MPS6, MPSVI, Maroteaux-Lamy disease, Mucopolysaccharidosis type VI, N-acetylgalactosamine 4-sulfatase deficiency
Drug discovery
8
drugs
With orphan designations
Overview
Mucopolysaccharidosis type VI (MPS VI/Maroteaux-Lamy syndrome) is an autosomal recessive lysosomal storage disorder caused by deficient arylsulfatase B activity, leading to dermatan sulfate accumulation. It manifests with progressive skeletal dysplasia (dysostosis multiplex), organomegaly, cardiac valve disease, corneal clouding, and respiratory complications, while typically sparing cognitive function. Diagnosis combines clinical evaluation, enzyme activity assays <10% normal [1][2][8], and genetic confirmation of ARSB mutations. Enzyme replacement therapy with galsulfase forms the cornerstone of disease-modifying treatment [1][3][16].
Burden
Functional: 55% school/work absenteeism [4], 78% need assistive mobility devices by adolescence [6][12]
Systemic: Spinal cord compression (34%), progressive valvulopathy (91%), corneal opacity (75%) [6][8][12]
Economic: Mean 3.9-year diagnostic delay [4][9], ERT interruptions in 44-48% due to access barriers [4]
Key monitoring includes annual cervical spine MRI, pulmonary function tests, and echocardiography [3][10]. Early ERT initiation correlates with improved growth velocity (Δ height Z-score +0.8) [13].
Therapies
ERT: Weekly IV galsulfase improves endurance (6MWT↑ 92m over 24 weeks [3]), reduces urinary GAGs [13], with long-term stabilization [16]
Adjuvant care: Orthopedic/cardiac surgeries (68% require ≥1 procedure [4]), CPAP for sleep apnea [3], corneal transplants [10]
Emerging approaches: HSCT preserves visceral/organ function but limited skeletal impact [16]
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare inborn errors of metabolism, rare ophthalmic disorders, rare transplant-related disorders
Research Papers
297 drug discovery papers about Mucopolysaccharidosis type 6, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
297 drug discovery papers about Mucopolysaccharidosis type 6, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-01 | Rare and rarer: percutaneous transcatheter mitral commissurotomy using over-the-wire technique in a patient with mucopolysaccharidosis—a case report
Abstract Background Percutaneous transcatheter mitral commissurotomy (PTMC) by the Inoue technique is the traditional technique to relieve rheumatic mitral stenosis. Mucopolysaccharidoses, a group of rare lysosomal storage disorders, result in skeletal and vertebral anomalies and cardiac valvular abnormalities. The coexistence of both pathologies is rare, and mitral stenosis in such a scenario may pose significant technical challenges. Case summary We present the case of a short statured 15-year-old girl with mucopolysaccharidosis Type VI with severe mitral stenosis and moderate aortic stenosis. Echocardiography revealed features suggestive of rheumatic involvement rather than due to the syndrome. Due to high surgical risk and unique anatomical characteristics, percutaneous approach was more amenable than surgery. The patient underwent successful PTMC using an unconventional over-the-wire technique instead of the traditional Inoue technique. Discussion This case highlights the importance of a case-based approach in unique anatomic and high-risk situations for better outcomes, which may need out-of-the-box thinking.
2026-06-19 | Anesthetic Management of Cesarean Section in a Patient With Mucopolysaccharidosis VI (MPS VI): A Case Report.
Mucopolysaccharidosis VI (MPS VI), a rare lysosomal storage disorder, leads to multisystem involvement (airway, skeletal, cardiac, and spinal pathologies) that significantly elevates anesthetic risks during cesarean delivery. A 29-year-old primigravida with MPS VI underwent clinically indicated elective cesarean section at 26 weeks' gestation due to progressive lower limb weakness that made her unable to tolerate continued pregnancy, following multidisciplinary obstetric and anesthesiology evaluation. Critical clinical features included extreme short stature, wheelchair dependence, macroglossia, severely restricted mouth opening (Mallampati class IV), and concomitant aortic valve disease. Ultrasound-guided continuous epidural anesthesia was administered through incremental injection of lidocaine carbonate, achieving adequate surgical anesthesia (T6 sensory level). The procedure was completed uneventfully, with hemodynamic stability and successful delivery of a viable neonate. This case demonstrates that continuous epidural anesthesia, when supported by comprehensive preoperative evaluation, ultrasound guidance, and contingency general anesthesia preparedness, represents a viable option for cesarean delivery in MPS VI patients.
2026-06-16 | A Rare Case of Mucopolysaccharidosis Presenting With Dysostosis Multiplex and Preserved Intelligence in a Seven-Year-Old Girl From Northeast India.
Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by a deficiency of enzymes required for the degradation of glycosaminoglycans (GAGs). These disorders are characterized by progressive multisystem involvement, including skeletal deformities, organomegaly, and variable neurocognitive impairment. We report a case of a seven-year-old girl presenting with recurrent respiratory complaints. Clinical examination revealed coarse facial features, short stature, short neck, hepatomegaly, joint stiffness, corneal clouding, and hearing impairment. Radiological findings showed features of dysostosis multiplex, including J-shaped sella turcica and oar-shaped ribs. Urinary GAG was positive. Cognitive function was normal. Based on clinical and investigative findings, a diagnosis of MPS type I-S (Scheie syndrome) or mild MPS type VI (Maroteaux-Lamy syndrome) was considered. This case highlights the importance of early clinical suspicion of MPS in children presenting with multisystem involvement and skeletal abnormalities, even in the presence of preserved intelligence. Early diagnosis is crucial for timely management and genetic counseling.
2026-05-18 | RPE Abnormality Is a Potential Primary Cause for Retinal Degeneration in Mucopolysaccharidosis Type VI Patients and a Rat Model.
Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in ARSB, leading to deficiency of N-acetylgalactosamine 4-sulfatase and accumulation of glycosaminoglycans. Although enzyme replacement therapy (ERT) alleviates systemic symptoms, its efficacy for ocular complications is limited. Because ocular manifestations may require distinct therapeutic approaches, a precise understanding of the underlying retinal pathology is essential. This study aimed to characterize ocular and retinal involvement in MPS VI through clinical and experimental analyses. Comprehensive ophthalmic examinations were performed in siblings with MPS VI, and histological and electrophysiological assessments were conducted in an MPS VI rat model. Retinal morphology, retinal pigment epithelium (RPE) integrity, and electroretinographic responses were evaluated. In patients, no apparent photoreceptor degeneration was detected, although subtle functional impairment could not be excluded. Consistently, MPS VI rats exhibited preserved photoreceptor structures but reduced electroretinogram amplitudes. Although RPE abnormalities were not evident in patients, rats showed pronounced RPE alterations, suggesting RPE involvement as a potential origin of retinal dysfunction. Our findings suggest that retinal dysfunction in MPS VI may primarily arise from RPE pathology rather than photoreceptor loss. Detailed retinal evaluations in aging patients are warranted, and therapeutic approaches targeting the RPE, such as localized ERT or RPE cell transplantation may provide future benefits.
2026-05-08 | Assessment of bone health and bone mineral density in patients with mucopolysaccharidosis receiving enzyme replacement therapy.
Most patients with mucopolysaccharidosis (MPS) experience skeletal involvement due to impaired bone remodeling, glycosaminoglycan (GAG) accumulation, reduced mobility, and nutritional deficiencies. These factors may predispose to low bone mass and increased fracture risk. This study assessed bone mineral density (BMD) using height-adjusted dual-energy X-ray absorptiometry (DXA) in pediatric MPS patients receiving enzyme replacement therapy (ERT) and examined its associations with clinical, functional, and biochemical parameters. This cross-sectional study included 29 children with biochemically and/or genetically confirmed MPS receiving ERT at Tanta University Hospital. Children under 5 years and ERT-naïve patients were excluded. BMD was measured at the lumbar spine (L1-L4) and femoral neck using DXA and adjusted for height-for-age z-score (HAZ). Clinical data, Katz Activities of Daily Living (ADL) score, anthropometry, and biochemical markers of bone metabolism were recorded. Statistical analyses included the Shapiro-Wilk test, Pearson correlation, and two-tailed t-test (p < 0.05). The cohort included 29 patients (19 males, 10 females; mean age 9.79 ± 3.85 years): 13 with MPS IVA, 11 with MPS I, 3 with MPS II, and 2 with MPS VI. Mean HAZ-adjusted BMD z-scores were - 1.84 ± 1.38 (right femur), - 2.07 ± 1.22 (left femur), and - 3.00 ± 1.49 (lumbar spine). Low bone mass for age (HAZ-adjusted z ≤ - 2) was present in 20/29 (68.9%) patients, predominantly affecting the spine. Vitamin D insufficiency/deficiency was observed in 75.9% of patients. Katz ADL score correlated strongly with BMD at all sites, particularly the lumbar spine (r = 0.88, p < 0.001). Total calcium and vitamin D levels showed positive correlations with BMD. Patients with cardiac involvement had significantly lower BMI than those without cardiac disease (p < 0.001). Pediatric patients with MPS receiving ERT show a high prevalence of low bone mass for age, driven by a multifactorial interaction between impaired mobility, nutritional deficiencies, and intrinsic skeletal pathology. Routine height-adjusted DXA monitoring, early physiotherapy, and proactive vitamin D and calcium supplementation should be integrated into comprehensive MPS care.
2026-07-01 | Rare and rarer: percutaneous transcatheter mitral commissurotomy using over-the-wire technique in a patient with mucopolysaccharidosis—a case report
Abstract Background Percutaneous transcatheter mitral commissurotomy (PTMC) by the Inoue technique is the traditional technique to relieve rheumatic mitral stenosis. Mucopolysaccharidoses, a group of rare lysosomal storage disorders, result in skeletal and vertebral anomalies and cardiac valvular abnormalities. The coexistence of both pathologies is rare, and mitral stenosis in such a scenario may pose significant technical challenges. Case summary We present the case of a short statured 15-year-old girl with mucopolysaccharidosis Type VI with severe mitral stenosis and moderate aortic stenosis. Echocardiography revealed features suggestive of rheumatic involvement rather than due to the syndrome. Due to high surgical risk and unique anatomical characteristics, percutaneous approach was more amenable than surgery. The patient underwent successful PTMC using an unconventional over-the-wire technique instead of the traditional Inoue technique. Discussion This case highlights the importance of a case-based approach in unique anatomic and high-risk situations for better outcomes, which may need out-of-the-box thinking.
2026-06-19 | Anesthetic Management of Cesarean Section in a Patient With Mucopolysaccharidosis VI (MPS VI): A Case Report.
Mucopolysaccharidosis VI (MPS VI), a rare lysosomal storage disorder, leads to multisystem involvement (airway, skeletal, cardiac, and spinal pathologies) that significantly elevates anesthetic risks during cesarean delivery. A 29-year-old primigravida with MPS VI underwent clinically indicated elective cesarean section at 26 weeks' gestation due to progressive lower limb weakness that made her unable to tolerate continued pregnancy, following multidisciplinary obstetric and anesthesiology evaluation. Critical clinical features included extreme short stature, wheelchair dependence, macroglossia, severely restricted mouth opening (Mallampati class IV), and concomitant aortic valve disease. Ultrasound-guided continuous epidural anesthesia was administered through incremental injection of lidocaine carbonate, achieving adequate surgical anesthesia (T6 sensory level). The procedure was completed uneventfully, with hemodynamic stability and successful delivery of a viable neonate. This case demonstrates that continuous epidural anesthesia, when supported by comprehensive preoperative evaluation, ultrasound guidance, and contingency general anesthesia preparedness, represents a viable option for cesarean delivery in MPS VI patients.
2026-06-16 | A Rare Case of Mucopolysaccharidosis Presenting With Dysostosis Multiplex and Preserved Intelligence in a Seven-Year-Old Girl From Northeast India.
Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by a deficiency of enzymes required for the degradation of glycosaminoglycans (GAGs). These disorders are characterized by progressive multisystem involvement, including skeletal deformities, organomegaly, and variable neurocognitive impairment. We report a case of a seven-year-old girl presenting with recurrent respiratory complaints. Clinical examination revealed coarse facial features, short stature, short neck, hepatomegaly, joint stiffness, corneal clouding, and hearing impairment. Radiological findings showed features of dysostosis multiplex, including J-shaped sella turcica and oar-shaped ribs. Urinary GAG was positive. Cognitive function was normal. Based on clinical and investigative findings, a diagnosis of MPS type I-S (Scheie syndrome) or mild MPS type VI (Maroteaux-Lamy syndrome) was considered. This case highlights the importance of early clinical suspicion of MPS in children presenting with multisystem involvement and skeletal abnormalities, even in the presence of preserved intelligence. Early diagnosis is crucial for timely management and genetic counseling.
2026-05-18 | RPE Abnormality Is a Potential Primary Cause for Retinal Degeneration in Mucopolysaccharidosis Type VI Patients and a Rat Model.
Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in ARSB, leading to deficiency of N-acetylgalactosamine 4-sulfatase and accumulation of glycosaminoglycans. Although enzyme replacement therapy (ERT) alleviates systemic symptoms, its efficacy for ocular complications is limited. Because ocular manifestations may require distinct therapeutic approaches, a precise understanding of the underlying retinal pathology is essential. This study aimed to characterize ocular and retinal involvement in MPS VI through clinical and experimental analyses. Comprehensive ophthalmic examinations were performed in siblings with MPS VI, and histological and electrophysiological assessments were conducted in an MPS VI rat model. Retinal morphology, retinal pigment epithelium (RPE) integrity, and electroretinographic responses were evaluated. In patients, no apparent photoreceptor degeneration was detected, although subtle functional impairment could not be excluded. Consistently, MPS VI rats exhibited preserved photoreceptor structures but reduced electroretinogram amplitudes. Although RPE abnormalities were not evident in patients, rats showed pronounced RPE alterations, suggesting RPE involvement as a potential origin of retinal dysfunction. Our findings suggest that retinal dysfunction in MPS VI may primarily arise from RPE pathology rather than photoreceptor loss. Detailed retinal evaluations in aging patients are warranted, and therapeutic approaches targeting the RPE, such as localized ERT or RPE cell transplantation may provide future benefits.
2026-05-08 | Assessment of bone health and bone mineral density in patients with mucopolysaccharidosis receiving enzyme replacement therapy.
Most patients with mucopolysaccharidosis (MPS) experience skeletal involvement due to impaired bone remodeling, glycosaminoglycan (GAG) accumulation, reduced mobility, and nutritional deficiencies. These factors may predispose to low bone mass and increased fracture risk. This study assessed bone mineral density (BMD) using height-adjusted dual-energy X-ray absorptiometry (DXA) in pediatric MPS patients receiving enzyme replacement therapy (ERT) and examined its associations with clinical, functional, and biochemical parameters. This cross-sectional study included 29 children with biochemically and/or genetically confirmed MPS receiving ERT at Tanta University Hospital. Children under 5 years and ERT-naïve patients were excluded. BMD was measured at the lumbar spine (L1-L4) and femoral neck using DXA and adjusted for height-for-age z-score (HAZ). Clinical data, Katz Activities of Daily Living (ADL) score, anthropometry, and biochemical markers of bone metabolism were recorded. Statistical analyses included the Shapiro-Wilk test, Pearson correlation, and two-tailed t-test (p < 0.05). The cohort included 29 patients (19 males, 10 females; mean age 9.79 ± 3.85 years): 13 with MPS IVA, 11 with MPS I, 3 with MPS II, and 2 with MPS VI. Mean HAZ-adjusted BMD z-scores were - 1.84 ± 1.38 (right femur), - 2.07 ± 1.22 (left femur), and - 3.00 ± 1.49 (lumbar spine). Low bone mass for age (HAZ-adjusted z ≤ - 2) was present in 20/29 (68.9%) patients, predominantly affecting the spine. Vitamin D insufficiency/deficiency was observed in 75.9% of patients. Katz ADL score correlated strongly with BMD at all sites, particularly the lumbar spine (r = 0.88, p < 0.001). Total calcium and vitamin D levels showed positive correlations with BMD. Patients with cardiac involvement had significantly lower BMI than those without cardiac disease (p < 0.001). Pediatric patients with MPS receiving ERT show a high prevalence of low bone mass for age, driven by a multifactorial interaction between impaired mobility, nutritional deficiencies, and intrinsic skeletal pathology. Routine height-adjusted DXA monitoring, early physiotherapy, and proactive vitamin D and calcium supplementation should be integrated into comprehensive MPS care.
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Drug Discovery Landscape
8 orphan drug designations for Mucopolysaccharidosis type 6, including 1 approved therapy.
8 orphan drug designations for Mucopolysaccharidosis type 6, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Pentosan polysulfate sodium | small molecules | EMA | 2020-08-21 | — | Paradigm Biopharmaceuticals (Ireland) Limited |
Odiparcil | small molecules | EMA | 2017-08-23 | — | Inventiva |
odiparcil | small molecules | FDA | 2017-08-03 | — | Inventiva SA |
pentosan polysulfate sodium | small molecules | FDA | 2015-01-05 | — | Paradigm Biopharmaceuticals Ltd. |
Adeno-associated viral vector containing the human ARSB gene | gene therapies | EMA | 2011-05-13 | — | Fondazione Telethon Ets |
adeno associated viral vector containing human ARSB gene | gene therapies | FDA | 2011-03-17 | — | Fondazione Telethon |
Galsulfase [Naglazyme] | proteins | EMA | 2001-02-14 | — | [INACTIVE] Biomarin Europe Limited |
N-acetylgalactosamine-4-sulfatase, recombinant human [Naglazyme] | proteins | FDA | 1999-02-17 | 2005-05-31 | BioMarin Pharmaceutical, Inc. |
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