Mucopolysaccharidosis type I Hurler/Scheie syndrome

A genetic disorder affecting the metabolism of glycosaminoglycans

Mucopolysaccharidosis type I Hurler/Scheie syndrome
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Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Developmental delay, skeletal abnormalities, heart disease
Complications	N/A
Onset	Infancy to early childhood
Duration	Lifelong
Types	N/A
Causes	Mutations in the IDUA gene
Risks	N/A
Diagnosis	Clinical evaluation, genetic testing
Differential diagnosis	N/A
Prevention	N/A
Treatment	Enzyme replacement therapy, hematopoietic stem cell transplantation
Medication	N/A
Prognosis	Variable, depending on severity
Frequency	Rare
Deaths	N/A

Mucopolysaccharidosis type I Hurler/Scheie syndrome (MPS I H/S) is a genetic disorder that affects the body's ability to break down certain complex carbohydrates known as glycosaminoglycans (GAGs). It is a subtype of Mucopolysaccharidosis type I (MPS I), which is caused by a deficiency of the enzyme alpha-L-iduronidase, encoded by the IDUA gene.

Pathophysiology

MPS I H/S is caused by mutations in the IDUA gene located on chromosome 4p16.3. This gene encodes the enzyme alpha-L-iduronidase, which is responsible for the degradation of dermatan sulfate and heparan sulfate, two types of glycosaminoglycans. In individuals with MPS I H/S, the deficiency of this enzyme leads to the accumulation of GAGs in lysosomes, causing cellular and tissue damage.

Clinical Features

The clinical presentation of MPS I H/S is intermediate between the severe form, Hurler syndrome, and the mild form, Scheie syndrome. Symptoms typically appear in early childhood and may include:

• Developmental delay and cognitive impairment
• Skeletal abnormalities such as joint stiffness and dysostosis multiplex
• Cardiac issues, including valvular heart disease
• Respiratory problems due to airway obstruction
• Corneal clouding and vision problems
• Hearing loss

Diagnosis

Diagnosis of MPS I H/S involves a combination of clinical evaluation, biochemical tests, and genetic testing. Enzyme assays can measure the activity of alpha-L-iduronidase in blood or fibroblasts. Genetic testing can confirm mutations in the IDUA gene.

Treatment

Treatment options for MPS I H/S include:

• Enzyme replacement therapy (ERT): Laronidase (Aldurazyme) is used to replace the deficient enzyme and reduce GAG accumulation.
• Hematopoietic stem cell transplantation (HSCT): This can provide a source of cells capable of producing the missing enzyme, potentially altering the disease course.
• Supportive care: Management of symptoms such as cardiac and respiratory issues, physical therapy, and surgical interventions for skeletal abnormalities.

Prognosis

The prognosis for individuals with MPS I H/S varies depending on the severity of the condition and the effectiveness of treatment. Early intervention with ERT and HSCT can improve outcomes and quality of life.

Also see

• Mucopolysaccharidosis type I
• Hurler syndrome
• Scheie syndrome
• Glycosaminoglycan
• Lysosomal storage disease