The mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders, caused by the deficiency of lysosomal enzymes needed to degrade glycosaminoglycan (GAG). Mucopolysaccharidosis type I (MPS I); also known as Hurler, Hurler-Scheie and Scheie syndrome, is an autosomal recessive disorder caused by the deficiency of an enzyme called alpha-L-iduronidase. Deficiency of this enzyme results in the accumulation of dermatan sulfate and heparan sulfate that are complex sugars known as glycosaminoglycans (GAGs). This deficiency, in turn, results in the accumulation of GAGs in the lysosomes leading to progressive, multi-system organ damage.
MPS I is relentlessly progressive and potentially fatal, although the severity of symptoms widely varies. It is categorized into Hurler syndrome (MPS IH), the most severe, Scheie syndrome (MPS IS), the mildest and Hurler-Scheie syndrome (MPS IHS), with an intermediate phenotype. In some patients the brain may be affected in combination with physical symptoms; others may develop physical symptoms with no brain involvement. Physical symptoms may include eye and hearing problems, bone and joint malformation, and heart and breathing difficulties. In Hurler syndrome the age of onset occurs 6-8 months after birth, with skeletal deformities and a delay in motor and intellectual development being the leading symptoms. Other symptoms may include corneal clouding, organomegaly, heart disease, short stature, hernias, facial dysmorphism and hirsutism. In Scheie syndrome, the adult-onset, patients are of almost normal height and do not show intellectual deficiency. Typical symptoms include stiff joints, corneal opacities, carpal tunnel syndrome and mild skeletal changes. Patients with Hurler-Scheie syndrome have normal or almost normal intelligence, but exhibit various degrees of physical impairment.