Hurler-Scheie syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Synonyms and keywords: MPS I H-S.

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 between the two extremes Hurler syndrome and Scheie syndrome. It is a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.

Hurler-Scheie syndrome is caused by mutations in the IDUA gene (4p16.3) leading to partial deficiency in the alpha-L-iduronidase enzyme and lysosomal accumulation of dermatan sulfate and heparan sulfate. Transmission is autosomal recessive.

Differential diagnoses include the milder and more severe forms of mucopolysaccharidosis type 1 (Scheie syndrome and Hurler syndrome respectively), mucopolysaccharidosis typeVI and mucopolysaccharidosis type II (see these terms).

The prevalence of MPS I has been estimated at 1/100,000, with Hurler-Scheie syndrome accounting for 23% of cases or a prevalence of approximately 1/435,000.

Life expectancy for Hurler-Scheie syndrome may be reduced, with death occurring before adolescence due to serious cardiovascular and respiratory complications.

Early diagnosis is difficult because the first clinical signs are not specific, but is very important to allow early treatment.

• Patients with Hurler-Scheie syndrome have normal or almost normal intelligence but exhibit various degrees of physical impairment.
• Patients present in the first years of life with musculoskeletal alterations to different degrees including
  • Short stature
  • Multiple dysostosis
  • Thoracic-lumbar kyphosis
  • Progressive coarsening of the facial features to different degrees
• Enlarged tonsils and adenoids
• Neurosensorial hearing loss

• Hydrocephaly can occur after the age of two.

• Short stature
• Thoracic-lumbar kyphosis

• Hirsutism may be a manifestation.

• Hydrocephaly can occur after the age of two.

• Corneal opacity is seen between two and four years of age and requires keratoplasty to restore sight.

• Neurosensorial hearing loss

• Nasal secretion

• Enlarged tonsils and adenoids

• Cardiomyopathy and valvular abnormalities

• Organomegaly may be a manifestation.
• Hernia may be a manifestation.

Diagnosis is based on detection of increased urinary secretion of heparan and dermatan sulfate through 1,9-dimethylmethylene blue test(DMB test) and glycosaminoglycan (GAG) electrophoresis, and demonstration of enzymatic deficiency in leukocytes or fibroblasts. Genetic testing is available.

Management should be carried out by a multidisciplinary team and should include physiotherapy to maintain range of movement.

The enzyme substitute (laronidase) given through weekly infusions 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.

Bone marrow or umbilical cord blood transplant has been successful and can preserve neurocognition, improve some aspects of the somatic disease and increase survival. However it is associated with many risks and most of the positive effects occur only if the procedure is performed in the first two years of life.

In individual patients with MPS1 of intermediate severity, HSCT may be considered if there is a suitable donor. There are however no data on the efficacy of HSCT in patients with this form of the disease.

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

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