Mucopolysaccharidosis Ih

=Mucopolysaccharidosis Type I (MPS I) = Mucopolysaccharidosis Type I (MPS I) is a rare genetic disorder that affects the body's ability to break down glycosaminoglycans (GAGs), which are long chains of sugar molecules used in the building of connective tissues. MPS I is part of a group of disorders known as lysosomal storage diseases.

Classification

MPS I is further classified into three subtypes based on the severity of symptoms:

• Hurler Syndrome (MPS I-H): The most severe form, characterized by developmental delay, organomegaly, and skeletal abnormalities.
• Hurler-Scheie Syndrome (MPS I-H/S): An intermediate form with symptoms that are less severe than Hurler syndrome but more severe than Scheie syndrome.
• Scheie Syndrome (MPS I-S): The mildest form, with symptoms that may not appear until later in childhood or adulthood.

Pathophysiology

MPS I is caused by mutations in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. This enzyme is responsible for breaking down GAGs such as dermatan sulfate and heparan sulfate. In individuals with MPS I, the deficiency of alpha-L-iduronidase leads to the accumulation of GAGs in lysosomes, causing cellular and tissue damage.

Symptoms

The symptoms of MPS I can vary widely depending on the subtype and may include:

• Developmental delay and intellectual disability
• Coarse facial features
• Enlarged liver and spleen (hepatosplenomegaly)
• Skeletal abnormalities (dysostosis multiplex)
• Joint stiffness and contractures
• Corneal clouding
• Hearing loss
• Cardiac issues

Diagnosis

Diagnosis of MPS I is typically based on clinical evaluation, biochemical tests to measure enzyme activity, and genetic testing to identify mutations in the IDUA gene. Newborn screening programs may also detect MPS I early in life.

Treatment

While there is no cure for MPS I, treatments are available to manage symptoms and improve quality of life:

• Enzyme Replacement Therapy (ERT): Administering synthetic alpha-L-iduronidase to reduce GAG accumulation.
• Hematopoietic Stem Cell Transplantation (HSCT): A potential treatment for severe cases, particularly Hurler syndrome, to provide a source of normal enzyme production.
• Supportive care, including physical therapy, surgery for skeletal abnormalities, and management of cardiac and respiratory issues.

Prognosis

The prognosis for individuals with MPS I varies depending on the subtype and the timing of treatment. Early intervention can improve outcomes, particularly in severe cases.

Research and Future Directions

Ongoing research aims to improve treatments for MPS I, including gene therapy and novel enzyme replacement strategies. Clinical trials are exploring the efficacy and safety of these approaches.

See Also

• Lysosomal storage disease
• Glycosaminoglycan
• Enzyme replacement therapy

NIH genetic and rare disease info

• NIH info on Mucopolysaccharidosis Ih

Mucopolysaccharidosis Ih is a rare disease.