Mucopolysaccharidosis type I (MPS I) is a rare inherited lysosomal storage disorder. It is due to the loss of function of alpha-L-iduronidase enzyme, resulting in the accumulation of two glycosaminoglycans (heparan sulfate and dermatan sulfate) in lysosomes. The abnormal activity of this enzyme has been associated with 3 different “forms” of diseases: the most severe early-onset form (Hurler’s syndrome), the milder form with generally adult onset (Scheie’s syndrome), and a form characterized by an intermediate phenotype (Hurler-Scheie syndrome).

The incidence of the severe form is about 1/100,000 while the incidence of the milder forms is about 1/500,000. However, recent studies have shown that the incidence of MSP I may be higher in certain populations. Despite the “classification” of the different forms of MPS I, patients often exhibit an extreme heterogeneity of symptomatology, thus it can be difficult to assign a patient to one of the three previously mentioned forms of MPS I. Generally, the symptomatology of MPS I includes: psychomotor retardation, skeletal deformities, facial dysmorphism, hernias (mainly inguinal and/or umbilical), hirsutism, corneal opacity, organomegaly, cardiac manifestations, carpal tunnel syndrome, recurrent infections of the airways and middle ear, short stature, and joint stiffness.

MPS I is an autosomal recessive disorder caused by mutations in the alpha-L-Iduronidase (IDUA) gene, located on the short arm of chromosome 4 (4p16.3). This gene extends for about 19 Kb, and contains 14 coding exons. Until now, more than a hundred mutations in this gene have been associated with MPS I. Since MPS I is inherited in an autosomal recessive manner, a patient must have causative mutations in both alleles of the IDUA gene. Usually, such mutations are inherited from both of the healthy parents, who are carriers of the mutated allele. Thus, if both parents are healthy carriers, they have a 25% probability of having affected offsprings, 50% of having children who are healthy carriers, and 25% of having healthy non-carrier children.

The suspected diagnosis of MPS I is confirmed or refuted by laboratory investigations. Typically, the first test measures the urinary heparan sulfate and dermatan sulfate levels. Even though this test is insufficient to confirm the suspected disease, it is still a good indication of the presence of disease. To confirm the clinical diagnosis, firstly, the activiy of alpha-L-iduronidase from dried blood spots is measured and, if positive, further confirmed by the sequencing of the IDUA gene.

Currently, two types of treatments are available: the allogeneic stem cells transplantation, and the administration of enzyme replacement therapy (ERT). The allogeneic stem cells transplantation is mainly performed for patients suffering from the severe form of MSP I (the transplant must be carried out within two years of life). Alternatively, the ERT is given for all patients who show significant benefits from this treatment. It has been shown that the earlier the treatment is given, the greater response and benefits from the treatment. However, ERT does not show significant efficacy on neurological lesions.