Abstract

Background: Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal genetic storage disorder caused by the accumulation of glycosaminoglycans in tissues and organs. A 10-month-old male with MPS VI had originally undergone foramen magnum decompression (FMD)/C1 followed by lifelong enzyme replacement therapy (ERT). At age 15, the patient underwent successful surgical treatment for retro-odontoid disease and recurrent cranio-cervical junction (CCJ) stenosis through a C1–C3 laminectomy and expansive duroplasty.

Case Description: A 10-month-old male with MPS VI and brain stem/spinal cord compression originally underwent a cervical FMD/C1 laminectomy. Despite ERT administration, signs of gait disturbances and myelopathy recurred before 1 year of age. At age 15, both computed tomography and magnetic resonance imaging revealed a retro-odontoid mass causing foramen magnum stenosis/upper cervical cord compression. Following an extended FMD that included a C1–C3 laminectomy and expansive duroplasty, his gait disturbance gradually improved.

Conclusion: Patients with MPS VI may experience recurrent CCJ stenosis and spinal cord compression despite the early initiation of ERT.

Keywords: Cranio-cervical junction, Enzyme replacement therapy, Foramen magnum decompression, Mucopolysaccharidosis VI, Spinal cord compression

INTRODUCTION

Mucopolysaccharidosis type VI (MPS VI, or Maroteaux-Lamy syndrome), an autosomal recessive lysosomal storage disorder, is caused by a deficiency of N-acetylgalactosamine-4-sulfatase. This enzymatic defect leads to the accumulation of glycosaminoglycans (GAGs) in tissues and organs, frequently resulting in progressive multisystem dysfunction.[ 1 , 3 , 8 ] Spinal cord compression at the cranio-cervical junction (CCJ) is one of the major clinical manifestations of MPS VI. Here, a 15-year-old male patient required repeated foramen magnum decompression (FMD), C1–C3 laminectomy, and duroplasty (i.e., he had an original FMD and C1 laminectomy at age 10 months) for recurrent myelopathy at CCJ stenosis attributed to MPS VI.

CASE DESCRIPTION

At 8 months of age, a patient with MPS IV underwent ventriculoperitoneal shunt placement for congenital hydrocephalus. At 10 months, he required FMD and C1 laminectomy for CCJ stenosis. Before the age of 1 year, enzyme replacement therapy (ERT) was initiated early, and maintained thereafter. At 14 years of age, he exhibited hyperreflexia and spasticity of both lower extremities. At age 15 years, he presented with a progressive quadriparesis and urinary dysfunction. Radiographs of the entire spine revealed skeletal dysplasia and dysmorphic vertebrae/instability [ Figure 1 ]. The cervical computed tomography (CT) showed foramen magnum stenosis and evidence of the prior FMD/C1 laminectomy. The cervical magnetic resonance imaging (MRI) confirmed the presence of a retro-odontoid mass compressing the CCJ [ Figure 1 ]. Repeat surgery included an extended FMD C1-C3 laminectomy, and an expansive duroplasty. The postoperative CT and MRI studies confirmed effective brain stem/spinal cord decompression, and his quadriparesis improved, enabling him to walk with assistance 1 week postoperatively [ Figure 2 ].

Figure 1:

Preoperative radiographs, CT and MRI scans. (a and b) Whole-spine radiographs demonstrating skeletal dysplasia and dysmorphic vertebrae. (c) Lateral radiograph in a neutral position, (d) in flexion, and (e) in extension. Cervical lateral radiographs did not reveal instability on flexion-extension imaging. (f) Three-dimensional CT image showing a narrowed foramen magnum and postoperative C1 laminectomy. (g) Whole-spine CT images demonstrating skeletal dysplasia and dysmorphic vertebrae. (h) Sagittal T2-weighted MRI showing spinal cord compression at the CCJ. CCJ: Cranio-cervical junction, CT: Computed tomography, MRI: Magnetic resonance imaging.

Figure 2:

Postoperative CT and MRI scans. (a and b) Three-dimensional CT and sagittal T2-weighted MRI demonstrating an expanded spinal canal and effective spinal cord decompression at the CCJ. CCJ: Cranio-cervical junction, CT: Computed tomography, MRI: Magnetic resonance imaging.

DISCUSSION

MPS VI is a rare disorder, with a prevalence of 0.36– 1.3/100,000 live births, accounting for approximately 1.7% of all MPS cases in Japan.[ 2 , 6 ] MPS VI, or Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4-sulfatase. This enzymatic defect leads to the accumulation of GAGs, particularly dermatan sulfate and chondroitin-4-sulfate, in various tissues and organs, resulting in progressive multisystem dysfunction.[ 1 , 3 , 8 ] Clinically, MPS VI presents as a multisystemic disorder characterized by skeletal abnormalities that may include short stature, dysostosis spinal cord compression, corneal clouding, cardiovascular and pulmonary complications, and hepatosplenomegaly. In MPS VI, spinal cord compression at the CCJ is attributed not only to osseous narrowing but also to soft-tissue masses surrounding the odontoid process, hypertrophy of the anterior/posterior longitudinal ligaments, and dural thickening resulting from GAG accumulation/fibrosis. ERT for MPS VI, introduced in 2005, has shown efficacy in slowing disease progression [ Table 1 ].[ 4 , 5 , 7 ] At age 15, this patient required a further extended FMD, including a C1–C3 laminectomy with duroplasty, to address recurrent myelopathy associated with MPS VI.

Table 1:

Summary of cases with ERT for MPS VI.

CONCLUSION

Patients with MPS VI may experience recurrent CCJ stenosis despite the early initiation of ERT.

Ethical approval:

The research/study approved by the Institutional Review Board at Kyoto Katsura Hospital, number 2025-16, dated March 26, 2025.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

References

1. Ceccarini R, Baldelli L, Padoan M, Paolini F, Brunasso L, Giovannini AE. Burden of surgical treatment for the management of cervical myelopathy in mucopolysaccharidoses: A systematic review. Brain Sci. 2023. 13: 48

2. D’Avanzo F, Zanetti A, De Filippis C, Tomanin R. Mucopolysaccharidosis type VI, an updated overview of the disease. Int J Mol Sci. 2021. 22: 13456

3. Harmatz P, Hendriksz CJ, Lampe C, McGill JJ, Parini R, LeãoTeles E. The effect of galsulfase enzyme replacement therapy on the growth of patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome). Mol Genet Metab. 2017. 122: 107-12

4. Horovitz DD, Magalhaes TS, Pena e Costa A, Carelli LE, Souza e Silva D, De Linhares e Riello AP. Spinal cord compression in young children with type VI mucopolysaccharidosis. Mol Genet Metab. 2011. 104: 295-300

5. Jurecka A, Opoka-Winiarska V, Jurkiewicz E, Marucha J, Tylki-Szymańska A. Spinal cord compression in Maroteaux-Lamy syndrome: Case report and review of the literature with effects of enzyme replacement therapy. Pediatr Neurosurg. 2012. 48: 191-8

6. Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M. Epidemiology of mucopolysaccharidoses. Mol Genet Metab. 2017. 121: 227-40

7. Pineda M, O’Callahghan M, Fenandez Lopez A, Coll MJ, Ullot R, Garcia-Fructuoso G. Clinical evolution after enzyme replacement therapy in twins with the severe form of Maroteaux-Lamy syndrome. JIMD Rep. 2016. 30: 7-14

8. Vairo F, Federhen A, Baldo G, Riegel M, Burin M, LeistnerSegal S. Diagnostic and treatment strategies in mucopolysaccharidosis VI. Appl Clin Genet. 2015. 8: 245-55