The animated videos in NORD’s Rare Disease Video Library provide brief introductions to rare disease topics for patients, caregivers, students, professionals and the public. NORD collaborates with medical experts, patient organizations, videographers and Osmosis to develop the videos, which are made possible by individual donations, educational grants and corporate sponsorships. NORD is solely responsible for the content.
Summary
Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder that affects many parts of the body (multisystem). Children with MPS I are described as having either a severe or attenuated (meaning reduced) form of the disorder based on age of onset, severity of symptoms, rate of disease progression and whether there is early and direct involvement of the brain. The determination of whether an individual has severe or attenuated MPS I is critical as different treatment options are available. Individuals with severe MPS I usually have symptoms apparent by 6 months of age whereas individuals with attenuated MPS I may not become apparent until after the age of 3 years with many attenuated MPS I individuals not diagnosed until late childhood or even the teenage years. Individuals with severe MPS I have onset of symptoms in early infancy with evidence of early progressive intellectual decline and when untreated, die within the first decade. In contrast, individuals with attenuated MPS I have later onset of disease symptoms, more slowly progressive disease with sparing of intelligence and can have a near normal life expectancy. MPS I is caused by variations (AKA mutations or pathogenic sequence variants) in the IDUA gene and is inherited in an autosomal recessive pattern. Therefore, both parents of every affected MPS I individual are carriers of MPS I. Being a carrier for MPS I does not lead to symptoms.
Introduction
MPS I is member of a group of hereditary metabolic diseases known as the mucopolysaccharidoses which, in turn, are part of a larger group of diseases known as lysosomal storage disorders (LSDs). Lysosomes function as the primary digestive and recycling units within cells. Enzymes within lysosomes break down or digest particular cellular components, such carbohydrates, proteins and fats to their basic units which can then be recycled. Healthy cells and organs are constantly breaking down, recycling and building new cellular components. In individuals with MPS disorders, including MPS I, deficiency or improper functioning of lysosomal enzymes leads to an abnormal accumulation of a particular complex carbohydrate known as glycosaminoglycans. Glycosaminoglycans were once known as mucopolysaccharides and are how these disorders got their names. When cells cannot breakdown these glycosaminoglycans they then accumulate within various tissues, such as the bones, joints, brain, spinal cord, heart, spleen, or liver and lead to the symptoms that MPS I individuals have.
MPS I is best thought of as a spectrum of disease that ranges from severe forms (Hurler syndrome) that are present very early in life to less severe forms that may not become apparent until much later in childhood. Individuals with MPS I were previously classified as having either a severe, mild, or intermediate form of the disorder. The severe form was known as Hurler syndrome, the mild form was known as Scheie syndrome, and the intermediate form was known as Hurler-Scheie syndrome. Although the term Hurler syndrome is still used, the term attenuated MPS I is now used in place of Hurler-Scheie and Scheie.
