Mucopolysaccharidosis Is

Mucopolysaccharidosis Type 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. This condition is part of a group of diseases known as lysosomal storage disorders.

Overview

MPS I is caused by a deficiency of the enzyme alpha-L-iduronidase, which is responsible for breaking down GAGs such as dermatan sulfate and heparan sulfate. The accumulation of these substances in the body's cells leads to a variety of symptoms and complications.

Classification

MPS I is traditionally divided into three subtypes based on severity:

• Hurler Syndrome (MPS I-H): The most severe form, characterized by developmental delay, skeletal abnormalities, and organ enlargement.
• 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 include joint stiffness and corneal clouding but normal intelligence.

Symptoms

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

• Skeletal abnormalities: Joint stiffness, short stature, and dysostosis multiplex.
• Neurological issues: Developmental delay, intellectual disability, and hydrocephalus.
• Organ involvement: Enlarged liver and spleen (hepatosplenomegaly), heart valve abnormalities.
• Ophthalmological issues: Corneal clouding and vision problems.
• Respiratory problems: Frequent upper respiratory infections and sleep apnea.

Diagnosis

Diagnosis of MPS I is typically based on clinical evaluation, family history, and laboratory tests. Enzyme assays can measure the activity of alpha-L-iduronidase in blood or fibroblasts. Genetic testing can confirm mutations in the IDUA gene.

Treatment

Treatment options for MPS I include:

• Enzyme Replacement Therapy (ERT): Laronidase (Aldurazyme) is used to replace the deficient enzyme.
• Hematopoietic Stem Cell Transplantation (HSCT): Can be considered, especially in severe cases, to provide a source of normal enzyme.
• Supportive care: Management of symptoms such as physical therapy, surgical interventions for skeletal abnormalities, and treatment of respiratory issues.

Prognosis

The prognosis for individuals with MPS I varies depending on the severity of the disease. Early diagnosis and treatment can improve quality of life and outcomes, particularly in less severe forms.

Research and Future Directions

Research is ongoing to develop new treatments, including gene therapy and substrate reduction therapy, which aim to address the underlying cause of the disease.

See Also

• Lysosomal storage disorders
• Glycosaminoglycans
• Enzyme replacement therapy

External Links

• [National MPS Society](https://mpssociety.org)
• Genetic and Rare Diseases Information Center

NIH genetic and rare disease info

• NIH info on Mucopolysaccharidosis Is

Mucopolysaccharidosis Is is a rare disease.