Mucopolysaccharidosis (MPS) is a rare genetic disorder in which specific enzymes within the lysosomes of cells are either deficient or functionally impaired, leading to the accumulation of glycosaminoglycans (GAGs) that are not properly degraded. MPS is a type of lysosomal storage disorder. Lysosomes are essential intracellular organelles responsible for breaking down waste and unnecessary substances within the cell. When lysosomal enzymes are deficient, GAGs progressively accumulate in tissues, impairing cellular function and causing pathological issues across multiple organ systems. Histologically, this GAG accumulation may result in cellular swelling, inflammatory responses, fibrosis, and deterioration of organ function.
Types of Mucopolysaccharidosis
MPS is classified into several subtypes based on the type of deficient enzyme and the causative gene, and most forms are inherited in an autosomal recessive manner. Only MPS II is inherited in an X-linked recessive pattern.
- MPS I (IDUA gene, α-L-iduronidase)
- MPS II (IDS gene, iduronate-2-sulfatase)
- MPS IIIA (SGSH gene, heparan-N-sulfatase)
- MPS IIIB (NAGLU gene, α-N-acetylglucosaminidase)
- MPS IIIC (HGSNAT gene, heparan-α-glucosaminide N-acetyltransferase)
- MPS IIID (GNS gene, N-acetylglucosamine-6-sulfatase)
- MPS IVA (GALNS gene, N-acetylgalactosamine-6-sulfatase)
- MPS IVB (GLB1 gene, β-galactosidase)
- MPS VI (ARSB gene, arylsulfatase B)
- MPS IX (HYAL1 gene, hyaluronidase 1)
Symptoms of Mucopolysaccharidosis
MPS throughout the body, leading to a wide range of symptoms. While the clinical presentation varies depending on the subtype, certain features are commonly shared. The nervous, musculoskeletal, cardiovascular, respiratory, and ocular systems are particularly affected.
Common Clinical Features
- Growth delay and short stature
- Coarse facial features
- Limited joint mobility, claw-like deformities of fingers and hands
- Kyphosis and cervical spinal stenosis
- Respiratory infections and respiratory tract obstruction
- Heart valve abnormalities
- Hepatomegaly and splenomegaly
- Hearing loss, visual impairment (including corneal clouding)
- Dental anomalies and gingival hypertrophy
Subtype-Specific Features
- MPS I (Hurler): Severe skeletal deformities, cognitive impairment, early death
- MPS II (Hunter): Intellectual disability and aggression, skin nodules, affects only males
- MPS III (Sanfilippo): Behavioral issues, sleep disturbances, autistic features, brain atrophy
- MPS IV (Morquio): Normal intelligence but severe skeletal abnormalities and significant physical limitation
- MPS VI (Maroteaux-Lamy): Severe kyphosis, visual impairment, normal intelligence
- MPS VII (Sly): Congenital anomalies, hydrops fetalis, severe multi-organ involvement
- MPS IX: Extremely rare; characterized by recurrent joint effusions and inflammation