Mucopolysaccharidoses (MPS)
General description
Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficiencies in specific enzymes responsible for the degradation of glycosaminoglycans (GAGs). These enzymatic defects lead to the accumulation of GAGs in various tissues, resulting in progressive multisystem involvement. The clinical spectrum and severity vary by subtype, but common features include skeletal deformities, organomegaly, cardiac abnormalities, and neurological impairment.
Subtypes
Each MPS subtype is defined by a specific enzyme deficiency, leading to the accumulation of particular GAGs in lysosomes:
- MPS I (Hurler, Hurler/Scheie, Scheie): Deficiency of α-L-iduronidase causes heparan sulfate and dermatan sulfate accumulation. This triggers cellular dysfunction and widespread organ involvement, including the brain and skeleton, leading to neurodegeneration, skeletal abnormalities, and multisystem disease.
- MPS II (Hunter): Caused by iduronate-2-sulfatase deficiency, resulting in heparan sulfate and dermatan sulfate storage. It is X-linked and primarily affects males. Disease severity ranges from severe neurodegenerative forms to attenuated somatic variants.
- MPS III (Sanfilippo): Encompasses four subtypes (A–D), each with a different enzyme deficiency, all impairing heparan sulfate degradation. The hallmark is progressive central nervous system dysfunction with relatively mild somatic features.
- MPS IV (Morquio): Subtypes A and B involve deficiencies in N-acetylgalactosamine-6-sulfate sulfatase or β-galactosidase, leading to keratan sulfate and chondroitin-6-sulfate accumulation. The primary manifestations are skeletal dysplasia and joint abnormalities, with little to no cognitive impairment.
- MPS VI (Maroteaux-Lamy): Due to N-acetylgalactosamine-4-sulfatase deficiency, causing dermatan sulfate accumulation. Patients have skeletal deformities and coarse facial features, often with preserved intelligence.
- MPS VII (Sly): β-glucuronidase deficiency leads to storage of several GAGs, including dermatan, heparan, and chondroitin sulfates. Clinical presentation ranges from severe (hydrops fetalis) to milder forms with cognitive impairment and skeletal disease.
- MPS IX (Hyaluronidase deficiency): Extremely rare, caused by hyaluronidase 1 deficiency, resulting in hyaluronic acid accumulation. Manifestations are typically mild, including periarticular masses and short stature.
References
- Zafeiriou, D. I., and S. P. Batzios. "Brain and spinal MR imaging findings in mucopolysaccharidoses: a review." American Journal of Neuroradiology 34.1 (2013): 5-13.
Virchow-Robin space
A characteristic MRI feature in MPS is the dilatation of perivascular (Virchow-Robin) spaces, which appear with cerebrospinal fluid-like signal intensity across all MRI sequences. These spaces often radiate from the subependymal region toward the cortex and are frequently observed in the periventricular and peritrigonal white matter, corpus callosum, basal ganglia, thalami, and brainstem. This finding is especially prominent in MPS type I (Hurler syndrome), whereas in MPS type II (Hunter syndrome), similar changes may be seen but are typically less pronounced and less progressive.
White matter changes
White matter changes are among the most common neuroimaging features in MPS. The periventricular white matter is particularly affected, often showing signal abnormalities alongside dilated Virchow-Robin spaces. These findings are frequently observed and considered characteristic in the neuroimaging of MPS patients.