Scheie syndrome

Scheie syndrome is a disease caused by a deficiency in the enzyme iduronidase, leading to the buildup of glycosaminoglycans (GAGs) in the body. It is the most mild subtype of mucopolysaccharidosis type I; the most severe subtype of this disease is called Hurler Syndrome.

Scheie syndrome is characterized by corneal clouding, facial dysmorphism, and normal lifespan. People with this condition may have aortic regurgitation.

Symptoms

The symptoms of Scheie syndrome are variable, but are milder than Hurler Syndrome. Symptoms may begin to appear by age 5, but affected children are often not diagnosed until after age 10. Patients with Scheie Syndrome may have normal intelligence, or they may have mild learning impairments or psychiatric problems. Glaucoma, retinal degeneration, and clouded corneas may cause visual impairments. Aortic valve disease may be present, along with carpal tunnel syndrome, deformed hands and feet, stiff joints, or sleep apnea. People with Scheie syndrome may live into adulthood.

Genetics

Scheie syndrome has an autosomal recessive pattern of inheritance.

Children with Scheie Syndrome carry two defective copies of the IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4. This is the gene which encodes for the protein iduronidase. All patients with subtypes of MPS I have mutations in the same gene, leading to deficiencies of the same enzyme. However, patients with Scheie Syndrome have a greater level of iduronidase activity than patients with Hurler Syndrome.

Because Scheie syndrome is an autosomal recessive disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a carriers. They will produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease.

History

In 1919, Gertrud Hurler, a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation. This became known as Hurler Syndrome. In 1962, a milder variant of Hurler Syndrome was identified by Scheie, leading to the designation of Scheie syndrome.

Diagnostic methods

• Early diagnosis is difficult because the first clinical signs are not specific, but is very important to allow early treatment.
• Diagnosis is based on detection of increased urinary secretion of heparan sulfate and dermatan sulfate through the 1,9-dimethylmethylene blue (DMB) test and glycosaminoglycan (GAG) electrophoresis, and demonstration of enzymatic deficiency in leukocytes or fibroblasts.
• Genetic testing is available.

Antenatal diagnosis Antenatal diagnosis is possible by measurement of enzymatic activity in cultivated chorionic villus or amniocyte and by genetic testing if the disease-causing mutation is known.

Treatment

• Management should be carried out by a multidisciplinary team and should include physiotherapy to maintain range of movement.
• The enzyme substitute (laronidase) obtained EU marketing authorization as an orphan drug in 2003.
• Given through weekly infusions it leads to improvement of lung function and joint mobility.
• [[Enzyme replacement therapy ] (ERT) should be started at diagnosis and may be beneficial in patients awaiting hematopoietic stem cell transplantation (HSCT).
• Early treatment slows the progression of the disease.

Prognosis

Life expectancy for patients with Scheie syndrome may only be slightly affected.

See also

• Hunter syndrome (MPS II)
• Sanfilippo syndrome (MPS III)
• Morquio syndrome (MPS IV)

External links

Classification	ICD-10: E76.0 OMIM: 607016
External resources	Orphanet: 93474