MPS I has an estimated prevalence of approximately 1 in 100,000 live births. The severe form (Hurler Syndrome) accounts for about 60% of cases, while milder forms occur less frequently. The disorder affects males and females equally and occurs across all ethnicities.

MPS I is caused by mutations in the IDUA gene located on chromosome 4 (4p16.3). This gene encodes the enzyme alpha-L-iduronidase, which is essential for breaking down GAGs. Mutations in this gene result in reduced or absent enzyme activity, leading to GAG accumulation in intracellular compartments called lysosomes and subsequent tissue damage. The disorder follows an autosomal recessive inheritance pattern, requiring two copies of the mutated gene for the condition to manifest (see RareShare Guide on Genetic Inheritance).

Symptoms of Hurler Syndrome, the most severe form of MPS I, typically manifest in early childhood between 6-12 months and may include:

• Coarse facial features (prominent forehead, wide nose, thick lips)

• Short stature and growth delays

• Joint stiffness and limited mobility

• Skeletal abnormalities (dysostosis multiplex)

• Hepatosplenomegaly (enlarged liver and spleen)

• Respiratory issues (obstructive sleep apnea, frequent infections)

• Cardiac abnormalities (valve issues)

• Hearing loss due to recurrent ear infections

• Corneal clouding

• Cognitive impairment and developmental delays, particularly in severe cases

Symptoms of the intermediate form (Hurler-Scheie Syndrome) appear later, typically around age 3-8, with milder cognitive and physical issues. For those with the attenuated form (Scheie Syndrome), symptoms typically emerge after age 5 with little impact on intelligence.

Diagnosis of MPS I involves clinical evaluation, biochemical testing and genetic analysis:

• A clinical assessment for symptoms and physical features (skeletal X-rays and heart, eye, hearing and cognitive tests).

• Urine GAG analysis to detect elevated levels of dermatan sulfate and heparan sulfate.

• Enzyme activity assay to measure alpha-L-iduronidase activity in blood or tissue samples.

• Genetic testing to identify IDUA gene mutations.

Currently, there is no cure for MPS I, and treatment focuses on managing symptoms and improving quality of life:

1. Enzyme Replacement Therapy (ERT): Laronidase (Aldurazyme) is administered intravenously to replace the deficient alpha-L-iduronidase enzyme.

2. Hematopoietic Stem Cell Transplantation (HSCT): To provide a source of enzyme-producing cells, considered for severe early diagnosed cases particularly before age 2.5 to improve outcomes.

3. Supportive Care: Includes physical and occupational therapy, cardiac management, hearing aids, and respiratory support.

4. Surgical Interventions: May be necessary for skeletal abnormalities or severe cardiac issues.

5. Emerging Therapies: Research is ongoing into potential gene therapy and substrate reduction therapy.

The prognosis for individuals with MPS I varies based on severity and timing of interventions. Without treatment, severe forms typically result in a shortened lifespan, often not extending beyond the second or third decade of life. Early diagnosis and treatment can significantly improve the quality of life and may extend life expectancy, especially in milder cases.

Providing a supportive and caring circle of friends and family greatly benefits the affected individual. Positive outlooks can help relieve frustration, devastation, and feeling of uncertainty experienced through living with Hurler syndrome. Genetic testing and counselling is recommended for at-risk families, to allow for more informed family planning.

1. Muenzer, J., Wrath, J.E. & Clarke, L.A. (2009). "Mucopolysaccharidosis I: management and treatment guidelines.” Pediatrics, 123(1), 19-29.

2. Pastores, G. M., Arn, P., Beck, M., Clarke, J.T., Guffon, N., Kaplan, P. & Wraith, J.E. (2007). "The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis TypeI." Molecular Genetics and Metabolism, 91(1), 37-47.

3. Aldenhoven, M., Wynn, R. F., Orchard, P. J., O'Meara, A., Veys, P., Fischer, A. & Boelens, J. J. (2015). "Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study." Blood, 125(13), 2164-2172.

4. Giugliani, R., Federhen, A., Rojas, M. V. M., Vieira, T., Artigalás, O., Pinto, L. L. & Martins, A. M. (2010). "Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment." Genetics and Molecular Biology, 33(4), 589-604.

5. Clarke, L. A., Wraith, J. E., Beck, M., Kolodny, E. H., Pastores, G. M., Muenzer, J. & Hopwood, J. J. (2009). "Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I." Pediatrics, 123(1), 229-240.

6. Orphanet: Mucopolysaccharidosis type 1.

7. NORD:  Mucopolysaccharidosis Type I.