Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that affects the body’s ability to break down certain long-chain sugar molecules known as glycosaminoglycans (GAGs). The disorder is caused by a defect in the IDUA gene, which provides instructions for producing the enzyme alpha-L-iduronidase. This enzyme plays a crucial role in breaking down two specific GAGs: dermatan sulfate and heparan sulfate. When alpha-L-iduronidase is deficient or absent, these GAGs accumulate inside lysosomes in cells throughout the body. Over time, this buildup causes progressive damage to tissues and organs, particularly affecting the skeletal system, heart, eyes, respiratory system, and central nervous system. MPS I exists along a clinical spectrum, ranging from severe to attenuated forms, depending on the level of residual enzyme activity.

Symptoms typically begin in early childhood, often within the first few years of life, and become progressively more severe. Children may develop: • Delayed development and intellectual disability • Coarse facial features • Short stature and growth delay • Joint stiffness and reduced mobility Other common features include: • Clouding of the cornea leading to vision impairment • Hearing loss and recurrent ear infections • Enlarged liver and spleen (hepatosplenomegaly) • Skeletal abnormalities (dysostosis multiplex) • Heart valve disease and cardiomyopathy • Chronic respiratory infections and airway obstruction In severe forms, progressive neurological decline occurs, often leading to loss of cognitive and motor function. Without treatment, life expectancy is significantly reduced.

MPS I is caused by mutations in the IDUA gene.

Diagnosis is based on: • Clinical evaluation and symptom recognition • Elevated GAGs in urine testing • Enzyme assays showing reduced alpha-L-iduronidase activity • Genetic testing to confirm IDUA mutations Prenatal testing is available when familial mutations are known.

There is no cure, but disease progression can be slowed. Treatment options include: • Enzyme replacement therapy (ERT) • Hematopoietic stem cell transplantation (HSCT) in selected patients • Multidisciplinary supportive care including physical therapy, cardiac monitoring, and respiratory support Early treatment improves outcomes significantly.