Scheie syndrome

Overview

Scheie syndrome is a rare genetic disorder and the mildest form of mucopolysaccharidosis type I (MPS I), a group of inherited metabolic conditions caused by the deficiency of a specific enzyme needed to break down glycosaminoglycans (GAGs). Named after Dr. Hermon Scheie, who first described the condition in the mid-20th century, this syndrome is characterized by a gradual buildup of GAGs in various tissues of the body. Unlike the severe forms of MPS I (Hurler and Hurler-Scheie syndromes), individuals with Scheie syndrome typically have normal intelligence and a longer life expectancy, although they may still experience significant physical complications.

Causes

Scheie syndrome is caused by mutations in the IDUA gene, which encodes the enzyme alpha-L-iduronidase. This enzyme is responsible for breaking down GAGs, specifically dermatan sulfate and heparan sulfate. When this enzyme is deficient or malfunctioning, these substances accumulate in cells, tissues, and organs, leading to progressive damage. The condition is inherited in an autosomal recessive manner, meaning that a child must inherit one defective copy of the gene from each parent to develop the syndrome.

Symptoms

The symptoms of Scheie syndrome usually become apparent in late childhood or adolescence and tend to progress slowly over time. Common clinical features include:

• Joint stiffness and limited range of motion, often affecting fingers, shoulders, and knees

• Carpal tunnel syndrome and other nerve entrapment issues

• Corneal clouding, which can impair vision

• Heart valve abnormalities, particularly aortic and mitral valve thickening or dysfunction

• Hernias (inguinal or umbilical)

• Coarse facial features, though less pronounced than in more severe MPS I forms

• Short stature and skeletal abnormalities (dysostosis multiplex)

• Mild respiratory difficulties due to airway thickening or stiffness of the chest wall

Importantly, individuals with Scheie syndrome typically maintain normal intelligence, distinguishing it from the more severe forms of MPS I that involve neurological impairment.

Diagnosis

Diagnosis of Scheie syndrome is based on clinical evaluation, biochemical tests, and genetic analysis. Key diagnostic steps include:

• Urine test: Detection of elevated levels of glycosaminoglycans (GAGs)

• Enzyme assay: Measuring the activity of alpha-L-iduronidase in blood or fibroblasts

• Genetic testing: Identification of mutations in the IDUA gene to confirm the diagnosis

• Imaging: X-rays to evaluate skeletal changes and echocardiograms for heart valve function

• Ophthalmologic exam: To assess corneal clouding and vision impairment

Early and accurate diagnosis is crucial for initiating appropriate treatment and monitoring the progression of the disease.

Treatment

While there is no cure for Scheie syndrome, several treatment options can manage symptoms and improve quality of life:

• Enzyme replacement therapy (ERT): Laronidase (Aldurazyme) is the FDA-approved treatment for MPS I. It replaces the deficient enzyme and helps reduce GAG accumulation in various tissues.

• Surgical interventions: May be needed for carpal tunnel syndrome, hernia repair, or heart valve replacement in severe cases.

• Physical therapy: To maintain joint flexibility and manage stiffness

• Ophthalmologic care: Monitoring and management of corneal clouding or glaucoma if present

• Cardiac care: Regular follow-ups to manage heart valve disease

A multidisciplinary approach involving geneticists, orthopedists, cardiologists, and other specialists is often required for comprehensive care.

Prognosis

The prognosis for individuals with Scheie syndrome is generally favorable compared to other forms of MPS I. With early diagnosis and appropriate management, many individuals can lead relatively normal lives and maintain independence. Life expectancy may be near normal, although complications related to heart disease, joint problems, or respiratory issues can impact quality of life. Ongoing advancements in enzyme therapy and supportive care continue to improve outcomes for those affected by this rare condition.