Hurler-Scheie syndrome: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
No edit summary
 
(7 intermediate revisions by one other user not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{SI}}
{{SI}}
{{CMG}}
{{CMG}}; {{AE}}


'''''Synonyms and keywords:'''''MPS I H-S.
'''''Synonyms and keywords:''''' MPS I H-S.


== Overview ==
== Overview ==
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. 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. 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. 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. 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 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 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. 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. Life expectancy for Hurler-Scheie syndrome may be reduced, with death occurring before adolescence due to serious cardiovascular and respiratory complications.
Hurler-Scheie syndrome is the intermediate form of [[Mucopolysaccharidosis#MPS I|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.
 
==Historical Perspective==
==Historical Perspective==


==Classification==
==Classifcation==


==Pathophysiology==
==Pathophysiology==
===Genetics===
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]].


=== Genetics ===
==Differentiating Hurler-Scheie syndrome from other Diseases==
Differential diagnoses include the milder and more severe forms of [[Mucopolysaccharidosis#MPS I|mucopolysaccharidosis type 1]] ([[Scheie syndrome]] and [[Hurler syndrome]] respectively), mucopolysaccharidosis typeVI and mucopolysaccharidosis type II (see these terms).


===Associated Conditions===
==Epidemiology and Demographics==


==Causes==
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.


==Differentiating type page name here from other Diseases==
==Risk Factors==


== Epidemiology and Demographics ==
==Screening==


== Risk Factors ==
==Natural History, Complications, and Prognosis==
Life expectancy for Hurler-Scheie syndrome may be reduced, with death occurring before adolescence due to serious cardiovascular and respiratory complications.


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


== Natural History, Complications, and Prognosis==
===History 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
*[[Enlarged tonsils]] and [[adenoids]]
*[[Neurosensorial hearing loss]]


== Diagnosis ==
*[[Hydrocephaly]] can occur after the age of two.


=== Symptoms ===
===Physical Examination===
====Appearence of the Patient====


===Family History===
*[[Short stature]]
*Thoracic-lumbar [[kyphosis]]


=== Physical Examination ===
====Skin====


==== Appearance of the Patient ====
*[[Hirsutism]] may be a manifestation.
 
====Vital Signs====
 
====Skin====


====Head====
====Head====


==== Eyes ====
*[[Hydrocephaly]] can occur after the age of two.
 
==== Ear ====


====Nose====
====Eyes====


====Throat ====
*[[Corneal opacity]] is seen between two and four years of age and requires [[keratoplasty]] to restore sight.


==== Heart ====
====Ear====


==== Lungs ====
*[[Neurosensorial hearing loss]]


==== Abdomen ====
====Nose====


==== Extremities ====
*Nasal secretion


==== Neurologic ====
====Throat ====


==== Other ====
*[[Enlarged tonsils]] and [[adenoids]]


=== Laboratory Findings ===  
====Heart====


==== Biomarker Studies ====
*[[Cardiomyopathy]] and [[valvular abnormalities]]


====CT ====
====Abdomen====


==== MRI ====
*[[Organomegaly]] may be a manifestation.
*[[Hernia]] may be a manifestation.


==== Ultrasound ====
===Laboratory Findings===  


== Treatment ==
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.
=== Pharmacotherapy ===


==== Acute Pharmacotherapies ====
===Imaging Findings===


==== Chronic Pharmacotherapies ====
===Other Diagnostic Studies===


=== Surgery and Device Based Therapy ===  
==Treatment==
Management should be carried out by a multidisciplinary team and should include [[physiotherapy]] to maintain range of movement.
===Medical Therapy===


==== Indications for Surgery ====
===Pharmacotherapy===
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.


==== Pre-Operative Assessment ====
===Surgery===  
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.


==== Post-Operative Management ====
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.
====Genetic Counseling====
Antenatal diagnosis is possible by measurement of enzymatic activity in cultivated [[chorionic villus]] or [[amniocyte]]s and by genetic testing if the disease-causing mutation is known. [[Genetic counseling]] is recommended.


===Primary Prevention===
===Primary Prevention===
====Genetic Counseling====
 
==Secondary Prevention===


==References==
==References==
Line 100: Line 117:
{{WikiDoc Sources}}
{{WikiDoc Sources}}


[[Category:Disease]]
[[Category:Endocrinology]]
[[Category:FLK]]

Latest revision as of 11:53, 22 July 2016

WikiDoc Resources for Hurler-Scheie syndrome

Articles

Most recent articles on Hurler-Scheie syndrome

Most cited articles on Hurler-Scheie syndrome

Review articles on Hurler-Scheie syndrome

Articles on Hurler-Scheie syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Hurler-Scheie syndrome

Images of Hurler-Scheie syndrome

Photos of Hurler-Scheie syndrome

Podcasts & MP3s on Hurler-Scheie syndrome

Videos on Hurler-Scheie syndrome

Evidence Based Medicine

Cochrane Collaboration on Hurler-Scheie syndrome

Bandolier on Hurler-Scheie syndrome

TRIP on Hurler-Scheie syndrome

Clinical Trials

Ongoing Trials on Hurler-Scheie syndrome at Clinical Trials.gov

Trial results on Hurler-Scheie syndrome

Clinical Trials on Hurler-Scheie syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Hurler-Scheie syndrome

NICE Guidance on Hurler-Scheie syndrome

NHS PRODIGY Guidance

FDA on Hurler-Scheie syndrome

CDC on Hurler-Scheie syndrome

Books

Books on Hurler-Scheie syndrome

News

Hurler-Scheie syndrome in the news

Be alerted to news on Hurler-Scheie syndrome

News trends on Hurler-Scheie syndrome

Commentary

Blogs on Hurler-Scheie syndrome

Definitions

Definitions of Hurler-Scheie syndrome

Patient Resources / Community

Patient resources on Hurler-Scheie syndrome

Discussion groups on Hurler-Scheie syndrome

Patient Handouts on Hurler-Scheie syndrome

Directions to Hospitals Treating Hurler-Scheie syndrome

Risk calculators and risk factors for Hurler-Scheie syndrome

Healthcare Provider Resources

Symptoms of Hurler-Scheie syndrome

Causes & Risk Factors for Hurler-Scheie syndrome

Diagnostic studies for Hurler-Scheie syndrome

Treatment of Hurler-Scheie syndrome

Continuing Medical Education (CME)

CME Programs on Hurler-Scheie syndrome

International

Hurler-Scheie syndrome en Espanol

Hurler-Scheie syndrome en Francais

Business

Hurler-Scheie syndrome in the Marketplace

Patents on Hurler-Scheie syndrome

Experimental / Informatics

List of terms related to 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.

Overview

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.

Historical Perspective

Classifcation

Pathophysiology

Genetics

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.

Differentiating Hurler-Scheie syndrome from other Diseases

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).

Epidemiology and Demographics

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.

Risk Factors

Screening

Natural History, Complications, and Prognosis

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

Diagnosis

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

Diagnostic Critera

History and Symptoms

Physical Examination

Appearence of the Patient

Skin

Head

Eyes

Ear

Nose

  • Nasal secretion

Throat

Heart

Abdomen

Laboratory Findings

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.

Imaging Findings

Other Diagnostic Studies

Treatment

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

Medical Therapy

Pharmacotherapy

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.

Surgery

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.

Genetic Counseling

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.

Primary Prevention

Secondary Prevention=

References


Template:WikiDoc Sources