Multilevel myelopathy in Maroteaux–Lamy syndrome and review of the literature

doi:10.1016/j.clineuro.2004.05.003

Clinical Neurology and Neurosurgery

Volume 107, Issue 3, April 2005, Pages 230-235

https://doi.org/10.1016/j.clineuro.2004.05.003 Get rights and content

Abstract

An 18-year-old male with Maroteaux–Lamy syndrome was presented with spastic quadriparesis. Magnetic resonance imaging of whole spinal canal revealed stenosis at multiple levels of cervical, thoracic and lumbar regions. By the guidance of combined evaluations of neurological examination, neuroradiological and electrophysiological findings, the most responsible spinal segment was detected each time he developed myelopathy and he underwent craniocervical, cervical and thoracolumbar decompressions consecutively. Ligamentum flavum hypertrophy was found to be the principal pathology responsible for the cord compression and myelopathy for all levels. The etiology of myelopathy and priority of the level for which decompression should be done in diffuse spinal stenosis were discussed with the literature review of Maroteaux–Lamy syndrome.

Introduction

The mucopolysaccharidoses are a group of inherited lysosomal storage diseases that cause disorders in the metabolism of mucopolysaccharides. Excess intracellular deposition of mucopolysaccharides within various connective tissues including the brain, dura mater, cerebral vasculature, and supporting ligaments accounts for the clinical manifestation of these disorders [1]. They are classified into seven syndromes according to the sort of enzyme deficiencies, the pattern of mucopolysacchariduria, and the clinical features [2].

Type VI mucopolysaccharidosis (MPS VI), or Maroteaux–Lamy syndrome, was first delineated by Maroteaux and Lamy in 1963 and is characterized by the accumulation of partially degraded dermatan sulfate due to the deficiency of the enzyme galactosamine-4-sulfate sulfatase (arylsulfatase B) [3]. Clinical features of MPS VI are growth retardation, facial dysmorphism, hirsutizm, corneal opacification, organomegaly, upper airway obstruction, cardiomyopathy, and valvular heart disease. Skelatal dysplasia can be pronounced and a number of patients have severe growth retardation secondary to widespread bony changes. Intellectual involvement is not a feature of this disease [1], [2].

Patients with MPS VI may need neurosurgical interventions for the hydrocephalus, spinal disorders and compressive neuropathies [1], [2], [4], [5], [6], [7], [8]. Spinal compressive myelopathy could particularly be complicated due to diffuse stenosis of whole spinal canal. We report the case of an 18-year-old patient with Maroteaux–Lamy syndrome who had complex neurological findings with the stenosis throughout the cervical, thoracic and lumbar regions due to the thickened ligamentum flavum documented in neuroradiological diagnostic measures. The role of electrophysiological studies is discussed in surgical timing and priority, and postoperative follow-up of affected spinal levels in MPS VI patients.

Section snippets

Case report

The 2-year-old male patient was first admitted to the hospital with delay in speech. Metabolic and genetic work-up resulted in the diagnosis of mucopolysaccharidosis type VI (Maroteaux–Lamy syndrome).

He re-admitted at age of 18 again with difficulty in walking, stiffness in lower extremities, and restriction of movement in his shoulders, elbows and knees.

He was consulted to neurosurgery with physical and neurological examination revealing typical physical and facial appearance of MPS VI. He had

Discussion

Patients with MPS VI may present with a wide spectrum of neurological symptoms. The disease involves the central nervous system and the musculoskeletal system. Patients with MPS VI may need neurosurgical interventions for the hydrocephalus, spinal disorders and compressive neuropathies [1], [2], [4], [5], [6], [7], [8].

Compression of the spinal cord is one of the major clinical features of MPS VI. Depositions of mucopolysaccharides in the dura mater and supporting ligaments, kyphoscoliosis, and

Conclusion

Since the quality of life and life expectancy of patients is improved after the transplantation, aggressive neurosurgical management of MPS VI associated pathologies is recommended. Insidious development of neurological symptoms and the dramatic improvement after neurosurgical intervention is impressive. Electrophysiological studies are useful in spinal canal stenosis for observing the clinical progression, deciding the surgical timing and level of compression, and postoperative follow-up of

References (15)

S.L. Wald et al.
Compressive myelopathy associated with type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)
Neurosurgery
(1984)
N. Tamaki et al.
Myelopathy due to diffuse thickening of the cervical dura mater in Maroteaux–Lamy syndrome: report of a case
Neurosurgery
(1987)
P. Maroteaux et al.
A new dystosis with urinary excretion of chondroitin-sulphate B
Presse Med.
(1963)
J.A. Thorne et al.
Craniovertebral abnormalities in type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)
Neurosurgery
(2001)
D.I. Peterson et al.
Myelopathy associated with Maroteaux–Lamy syndrome
Arch. Neurol.
(1975)
R. Young et al.
Compressive myelopathy in Maroteaux–Lamy syndrome: clinical and pathological findings
Ann. Neurol.
(1980)
V.I. Vougioukas et al.
Neurosurgical interventions in children with Maroteaux–Lamy syndromeCase report and the review of the literature
Pediatr. Neurosurg.
(2001)

There are more references available in the full text version of this article.

Cited by (54)

Cranio-cervical decompression associated with non-instrumented occipito-C2 fusion in children with mucopolysaccharidoses: Report of twenty-one cases
2022, North American Spine Society Journal
Mucopolysaccharidosis (MPS) is a multisystemic storage disorder of glycosaminoglycan deposits. Infiltration of the dura mater and supporting ligaments caused spinal cord compression and consecutive myelopathy, especially at the cranio-cervical junction (CCJ). Craniocervical instability and posterior decompression often raise the problem of fixation in children. The main purpose of this paper was to report the result of an original technique of occipito-cervical arthrodesis using a cranial halo-cast system in pediatric population.
We recorded 21 patients with cervical myelopathy. All of them had spinal cord decompression by enlargement of the foramen magnum, C1 laminectomy, and occipito-C2 fusion using corticocancellous bone graft. Only one child has an extended laminectomy from C1 to C3. The occiput-C2 arthrodesis was stabilized by the cranial halo-cast system. This immobilization was performed preoperatively and kept for three months then switched to rigid cervical collar. Clinical assessment, including the Goel grade and mJOA, radiographs and magnetic resonance imaging were performed before surgery. The occipito-cervical arthrodesis was controlled by standard X-rays and CT scan.
According to the type of mucopolysaccharidosis, the patients were divided into MPS type I: n= 3, II: n=7, IV: n=11. The mean age of patients at surgery was 6.76 years. All mucopolysaccharidoses cases required a foramen magnum decompression by craniectomy, C1 laminectomy and occipito-C2 arthrodesis. As major complications, a child had immediate post-operative paraplegia due to spinal cord ischemia. The postoperative follow-up ranged from 1.5 to 4 years, with an average of 3.3 years. The average preoperative mJOA score was 8.9, and it improved to 14 points at the last follow-up.
Satisfactory fusion and good clinical results were obtained with the 2-stage approach to CCJ anomalies.
Generation of a novel disease model mouse for mucopolysaccharidosis type VI via c. 252T>C human ARSB mutation knock-in
2022, Biochemistry and Biophysics Reports
Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal disorder caused by a mutation in the ARSB gene, which encodes arylsulfatase B (ARSB), and is characterized by glycosaminoglycan accumulation. Some pathogenic mutations have been identified in or near the substrate-binding pocket of ARSB, whereas many missense mutations present far from the substrate-binding pocket. Each MPS VI patient shows different severity of clinical symptoms. To understand the relationship between mutation patterns and the severity of MPS VI clinical symptoms, mutations located far from the substrate-binding pocket must be investigated using mutation knock-in mice. Here, I generated a knock-in mouse model of human ARSB Y85H mutation identified in Japanese MPS VI patients using a CRISPR-Cas9-mediated approach. The generated mouse model exhibited phenotypes similar to those of MPS VI patients, including facial features, mucopolysaccharide accumulation, and smaller body size, suggesting that this mouse will be a valuable model for understanding MPS VI pathology.
Mucopolysaccharidoses
2020, Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Metabolic Disorders
The mucopolysaccharidoses (MPSs) are inherited disorders of the metabolism of the glycosaminoglycans (GAGs), caused by the deficiency of enzymes involved in the stepwise degradation of these compounds. Being the GAGs a major component of the extracellular matrix of the connective tissue, its storage leads to a multisystem disorder. Eleven subtypes of MPS have been described so far, being all chronic and progressive, having a wide range of clinical manifestations and a broad spectrum of severity in each type. The disease generally presents in one of the three ways depending on the specific enzyme that is defective: (1) A dysmorphic syndrome (e.g., MPS types I, II, VI, or VII); (2) behavioral disturbances, neurodegeneration, and dementia (MPS III); (3) a severe bone dysplasia (MPS IV). In most cases, diagnosis initially depends on clinical suspicion, followed by demonstration of increased levels and/or abnormal pattern of GAGs in urine. The clinical picture combined with the pattern of urinary GAG excretion usually guides the laboratory to define which specific enzymes should be analyzed in order to identify the deficiency and elucidate the diagnosis. Mutation analyses are recommended to pinpoint the specific genetic defects causing the disorder. Although no cure exists for the MPSs, several treatment approaches are available or under investigation. Management is multidisciplinary and includes palliative care, surgeries, cell-based therapy (bone marrow or umbilical cord blood transplantation) and enzyme replacement therapy (ERT). Manifestations involving the skeleton and particularly the central nervous system (CNS) are the most challenging to treat, but newer therapeutic approaches (e.g., substrate reduction, Trojan horse ERT, intrathecal (IT)/ intracerebroventricular ERT, stop codon read-through, gene therapy, gene editing, etc.) are in development and may change the outcome of these disorders in a near future. Carrier identification and prenatal diagnosis are available for all of these disorders, and newborn screening (NBS) is already being conducted as part of regular programs for MPS I and MPS II in some places, and is under investigation for other treatable MPSs.
Clinical Manifestations and Surgical Management of Spinal Lesions in Patients With Mucopolysaccharidosis: A Report of 52 Cases
2019, Spine Deformity
Citation Excerpt :
Neurologically intact patients are assessed through clinical and imaging studies, and surgery is indicated when pathologic findings appear [9,15]. Spinal cord myelomalacia associated with stenosis of the cervical canal is a very common finding in MPS [5,16,17]. Our series of eight patients presented myelomalacia, three with dynamic C1–C2 instability and five with static stenosis secondary to GAG deposits.
Descriptive retrospective cohort of 52 pediatric patients with mucopolysaccharidosis (MPS) and spinal cord disease and surgical outcomes in a reference hospital.
To describe clinical manifestations and surgical management and outcomes of spinal lesions.
All medical records of 52 patients with mucopolysaccharidosis (I, II, III, IV, and VI) diagnosed between 1992 and 2011 were identified and followed at a single spine center of a pediatric hospital. Demographic, clinical manifestations, spinal cord lesions, and surgical management were the focus of the descriptive report.
A total of 52 patients (32 males and 20 females), mean age at diagnosis of 8 ± 4 years (range 1–19), and with a mean follow-up of 11 ± 8 years were identified. Forty-three had cervical disease (the most frequent affection found was odontoid hypoplasia followed by atlantoaxial instability) and 14 patients had thoracolumbar kyphosis. Twenty-one patients presented neurologic compromise before surgery (quadriparesis as the most frequent manifestation), with the progression of neurologic impairment being the most common surgical indication. Surgery was performed in 38 patients (25 cervical and 13 thoracolumbar). Of the 21 patients with preoperative neurologic deficit, 6 patients showed neurologic improvement. The most common surgical complication found was proximal junctional kyphosis.
This is the largest series published of mucopolysaccharidosis pediatric patients with a surgically treated spinal condition. We recommend early spinal cord decompression in mucopolysaccharidosis spine pathology to prevent or potentially reverse neurologic impairment.
Level IV.
Surgical management of neurological manifestations of mucopolysaccharidosis disorders
2017, Molecular Genetics and Metabolism
The mucopolysaccharidosis (MPS) disorders are ultra-rare lysosomal storage disorders associated with progressive accumulation of glycosaminoglycans (GAGs) in cells and tissues throughout the body. Clinical manifestations and progression rates vary widely across and within the different types of MPS. Neurological symptoms occur frequently, and may result directly from brain damage caused by infiltration of GAGs, or develop secondary to somatic manifestations such as spinal cord compression, hydrocephalus, and peripheral nerve entrapment. Management of secondary neurological manifestations often requires surgical correction of the underlying somatic cause. The present review discusses the surgical management of neurological disease in patients with MPS, including diagnostic imaging. Background information is derived from presentations and discussions during a meeting on the brain in MPS, attended by an international group of experts (April 28–30, 2016, Stockholm, Sweden), and additional literature searches.
Unique medical issues in adult patients with mucopolysaccharidoses
2016, European Journal of Internal Medicine
The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2–4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.

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Case reportMultilevel myelopathy in Maroteaux–Lamy syndrome and review of the literature

Abstract

Introduction

Section snippets

Case report

Discussion

Conclusion

Compressive myelopathy associated with type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)

Neurosurgery

Myelopathy due to diffuse thickening of the cervical dura mater in Maroteaux–Lamy syndrome: report of a case

Neurosurgery

A new dystosis with urinary excretion of chondroitin-sulphate B

Presse Med.

Craniovertebral abnormalities in type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)

Neurosurgery

Myelopathy associated with Maroteaux–Lamy syndrome

Arch. Neurol.

Compressive myelopathy in Maroteaux–Lamy syndrome: clinical and pathological findings

Ann. Neurol.

Neurosurgical interventions in children with Maroteaux–Lamy syndromeCase report and the review of the literature

Pediatr. Neurosurg.

Case report
Multilevel myelopathy in Maroteaux–Lamy syndrome and review of the literature