Hurler–Scheie syndrome

Overview

Hurler–Scheie syndrome is a form of mucopolysaccharidosis type I (MPS I), representing an intermediate severity between the severe Hurler syndrome and the milder Scheie syndrome. It is a progressive, inherited metabolic disorder caused by partial deficiency of the enzyme alpha-L-iduronidase. This enzyme is responsible for breaking down glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate. In Hurler–Scheie syndrome, the reduced enzyme activity leads to accumulation of GAGs in various tissues, causing multi-system complications over time. The condition typically becomes evident in early childhood and progresses more slowly than classic Hurler syndrome.

Causes

Hurler–Scheie syndrome is caused by mutations in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. The disorder follows an autosomal recessive inheritance pattern, meaning that two defective copies of the gene (one from each parent) are required for the condition to manifest. The enzyme deficiency is not complete, which differentiates Hurler–Scheie syndrome from the more severe Hurler form.

Symptoms

Symptoms of Hurler–Scheie syndrome often begin in early childhood and may include:

• Coarse facial features

• Joint stiffness and limited mobility

• Short stature and growth delay

• Corneal clouding leading to visual impairment

• Hearing loss

• Cardiac issues, particularly valvular heart disease

• Hernias (inguinal or umbilical)

• Enlarged liver and spleen (hepatosplenomegaly)

• Mild to moderate developmental delay (though some individuals have normal intelligence)

Unlike Hurler syndrome, severe cognitive decline is less common, and lifespan can extend into adulthood with proper care.

Diagnosis

Diagnosis of Hurler–Scheie syndrome is based on clinical evaluation, biochemical testing, and genetic analysis. Key diagnostic tools include:

• Urinary GAG analysis: Elevated levels of dermatan sulfate and heparan sulfate

• Enzyme assay: Reduced alpha-L-iduronidase activity in blood or fibroblasts

• Genetic testing: Detection of mutations in the IDUA gene

• Imaging studies: X-rays may show skeletal abnormalities (dysostosis multiplex)

• Eye and heart evaluations: To assess corneal clouding and valvular disease

Early diagnosis allows for timely initiation of treatment and management of complications.

Treatment

Treatment for Hurler–Scheie syndrome focuses on reducing GAG accumulation and managing symptoms. Therapeutic options include:

• Enzyme Replacement Therapy (ERT): Laronidase (Aldurazyme) is used to supplement the deficient enzyme and improve systemic symptoms

• Surgical interventions: May be necessary for hernias, joint contractures, or corneal clouding

• Cardiac care: Monitoring and treatment for valvular disease

• Supportive care: Physical therapy, occupational therapy, hearing aids, and visual aids

Hematopoietic stem cell transplantation (HSCT) is less commonly used in Hurler–Scheie patients due to milder neurological involvement.

Prognosis

The prognosis for individuals with Hurler–Scheie syndrome is generally better than for those with classic Hurler syndrome. With appropriate treatment, many patients can lead productive lives into adulthood. However, the condition remains progressive, and untreated complications can impair quality of life. Early diagnosis and lifelong multidisciplinary care are essential to managing symptoms, slowing progression, and improving long-term outcomes.