Hurler–Scheie syndrome

Other Names: Mucopolysaccharidosis Ih/s ; MPS1-HS; MPS1H/S; Mucopolysaccharidosis type 1H/S; Mucopolysaccharidosis type IH/S; Hurler-Scheie syndrome; MPSIH/S

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1 ) 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.

Epidemiology

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.

Cause

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

Transmission is autosomal recessive. Genetic counseling is recommended.

Signs and symptoms

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, cardiomyopathy and valvular abnormalities, neurosensorial hearing loss, enlarged tonsils and adenoids, and nasal secretion. 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. Other manifestations may include organomegaly, hernias and hirsutism.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormal heart valve morphology
• Abnormal vertebral morphology
• Abnormality of the tonsils
• Coarse facial features(Coarse facial appearance)
• Corneal opacity
• Hepatomegaly(Enlarged liver)
• Hernia
• Limitation of joint mobility(Decreased joint mobility)
• Rhinitis(Nasal inflammation)
• Short stature(Decreased body height)
• Skeletal dysplasia
• Splenomegaly(Increased spleen size)

30%-79% of people have these symptoms

• Abnormal nerve conduction velocity
• Abnormal pyramidal sign
• Sensorineural hearing impairment
• Spinal canal stenosis(Narrow spinal canal)

5%-29% of people have these symptoms

• Cardiomyopathy(Disease of the heart muscle)
• Generalized hirsutism(Excessive hairiness over body)

Diagnosis

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 and dermatan sulfate through 1,9-dimethylmethylene blue (DMB) test and glycosaminoglycan (GAG) electrophoresis, and demonstration of enzymatic deficiency in leukocytes or fibroblasts. Genetic testing is available.

Differential diagnosis 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).

Antenatal diagnosis 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.

Treatment

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

Prognosis

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