Hurler–Scheie syndrome

Title

Other Names:

Mucopolysaccharidosis Ih/s ; MPS1-HS; MPS1H/S; Mucopolysaccharidosis Ih/s ; MPS1-HS; MPS1H/S; Mucopolysaccharidosis type 1H/S; Mucopolysaccharidosis type IH/S; Hurler-Scheie syndrome; MPSIH/S See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Congenital and Genetic Diseases; Eye diseases; Heart Diseases; Metabolic disorders; Musculoskeletal Diseases; Nervous System Diseases See More

This disease is grouped under:

Mucopolysaccharidosis type I

Summary Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 93476

Definition

Hurler-Scheie syndrome is the intermediate form of mucopolysaccharidosis type 1 (MPS1; see this term) between the two extremes Hurler syndrome and Scheie syndrome (see these terms); 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.

Clinical description

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.

Etiology

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.

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 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.

Genetic counseling

Transmission is autosomal recessive. Genetic counseling is recommended.

Management and 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.

Visit the Orphanet disease page for more resources.

Last updated: 10/1/2011

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal heart valve morphology		0001654
Abnormal vertebral morphology		0003468
Abnormality of the tonsils		0100765
Coarse facial features	Coarse facial appearance	0000280
Corneal opacity		0007957
Hepatomegaly	Enlarged liver	0002240
Hernia		0100790
Limitation of joint mobility	Decreased joint mobility Decreased mobility of joints Limited joint mobility Limited joint motion [ more ]	0001376
Rhinitis	Nasal inflammation	0012384
Short stature	Decreased body height Small stature [ more ]	0004322
Skeletal dysplasia		0002652
Splenomegaly	Increased spleen size	0001744
30%-79% of people have these symptoms
Abnormal nerve conduction velocity		0040129
Abnormal pyramidal sign		0007256
Sensorineural hearing impairment		0000407
Spinal canal stenosis	Narrow spinal canal	0003416
5%-29% of people have these symptoms
Cardiomyopathy	Disease of the heart muscle	0001638
Generalized hirsutism	Excessive hairiness over body	0002230
Percent of people who have these symptoms is not available through HPO
Aortic regurgitation		0001659
Autosomal recessive inheritance		0000007
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Dysostosis multiplex		0000943
Hirsutism	Excessive hairiness	0001007
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Kyphosis	Hunched back Round back [ more ]	0002808
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Mitral regurgitation		0001653
Obstructive sleep apnea		0002870
Pulmonary arterial hypertension	Increased blood pressure in blood vessels of lungs	0002092
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Scoliosis		0002650
Thick vermilion border	Full lips Increased volume of lip Plump lips Prominent lips Thick lips [ more ]	0012471
Thickened skin	Thick skin	0001072
Tracheal stenosis	Narrowing of windpipe	0002777
Umbilical hernia		0001537

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Last updated: 2/1/2021

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Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Orphan Disease Center: MPS I Pilot Grant Program presents a request for applications (RFA) to support research on the development of improved therapies for people with syndromes due to MPS I including Hurler, Hurler-Scheie and Scheie. All individuals holding a faculty-level appointment at an academic or non-profit institution are eligible to respond to this RFA. Grants will be awarded for an initial period of 1 to 2 years at $150,000 direct costs per year (up to 10% indirect costs allowable); funding for a second year is predicated by adequate progress during year 1 and availability of funding. All applicants must first submit a letter of Interest (LOI) to be reviewed for consideration of a full application submission. LOIs are due no later than Monday, February 29, 2016 at 5pm (EST).

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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