Prevalence and Incidence • Estimated incidence of 1 in 100,000 to 1 in 170,000 live births. • Estimated prevalence of 1 in 500,000.  • It is a pan-ethnic disease that affects males and females.
	Age of onset The age of onset of MPS I varies depending on the severity of the disorder. Symptoms may be more subtle and mistakenly be attributed to other more prevalent disorders, arriving at a final diagnosis until later in childhood or even adulthood.

 

MPS I disease presents a broad clinical variability, and manifestations will differ both in severity and age of onset. Patients usually present themselves with a constellation of symptoms and signs, affecting several organs and systems.  

Common symptoms include:

• Skeletal abnormalities, including spinal deformities, claw hands, an enlarged skull, spinal deformities, and dysostosis multiplex. 
• Facial dysmorphism: prominent foreheads, flat nose bridge, anteverted nostrils, enlarged lips, macroglossia, and spaced and protruded eyes.
• Airway obstruction. 
• Hepatosplenomegaly.
• Corneal clouding. 
• Inguinal hernia.
• Carpal tunnel syndrome.
• Failure to thrive.

Patients may also experience recurrent ear and respiratory infections, and sleep apnea. In severe patients, neurological symptoms such as developmental delay, cognitive impairment, and hearing loss may be developed within the first year of life.

These severe patients may also develop hydrocephalus and experience progressive neurodegeneration.

Enzyme activity assays, performed on leukocytes, fibroblasts, or plasma, can confirm the deficiency of α-L-iduronidase enzyme activity and diagnose the disease.

Genetic testing can detect IDUA gene variations, which will additionally help assess the phenotype of the disease in some cases, which is particularly important in infants and toddlers to define the therapeutic approach.

Enzyme replacement therapy (ERT) is the treatment of choice that addresses several of the non-neurological manifestations of the MPS I disease. It has been found to provide significant clinical benefits including improved pulmonary function, enhanced walking ability, and decreased organ glycosaminoglycan accumulation. However, it is ineffective in treating the neurodegenerative aspects of the disease.

In severe patients diagnosed before 24 months of age with preserved cognition, hematopoietic stem cell transplantation is the treatment of choice when it is available. This procedure should be performed by an experienced multidisciplinary team. It is important to highlight that severe patients may benefit from a period of peri transplant ERT, to improve some somatic manifestations of the disease and obtain better results with the transplant. Usually, ERT is maintained until engraftment is documented.
 

MPS I disease can cause corneal clouding, which may result in blindness if untreated.