Hurler-Scheie syndrome: Difference between revisions
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'''''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#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. | 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== | ||
== | ==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]]. | 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== | |||
==Differentiating | |||
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). | 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). | ||
== Epidemiology and Demographics == | ==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. | 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. | Life expectancy for Hurler-Scheie syndrome may be reduced, with death occurring before adolescence due to serious cardiovascular and respiratory complications. | ||
== Diagnosis == | ==Diagnosis== | ||
Early diagnosis is difficult because the first clinical signs are not specific, but is very important to allow early treatment. | Early diagnosis is difficult because the first clinical signs are not specific, but is very important to allow early treatment. | ||
===Diagnostic Critera=== | |||
=== Symptoms === | ===History and Symptoms=== | ||
*Patients with Hurler-Scheie syndrome have normal or almost normal [[intelligence]] but exhibit various degrees of physical impairment. | *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 | *Patients present in the first years of life with musculoskeletal alterations to different degrees including | ||
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*[[Hydrocephaly]] can occur after the age of two. | *[[Hydrocephaly]] can occur after the age of two. | ||
=== Physical Examination === | ===Physical Examination=== | ||
====Appearence of the Patient==== | |||
==Appearence of the Patient== | |||
*[[Short stature]] | *[[Short stature]] | ||
*Thoracic-lumbar [[kyphosis]] | *Thoracic-lumbar [[kyphosis]] | ||
==Skin== | ====Skin==== | ||
*[[Hirsutism]] may be a manifestation. | *[[Hirsutism]] may be a manifestation. | ||
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*[[Hydrocephaly]] can occur after the age of two. | *[[Hydrocephaly]] can occur after the age of two. | ||
==== Eyes ==== | ====Eyes==== | ||
*[[Corneal opacity]] is seen between two and four years of age and requires [[keratoplasty]] to restore sight. | *[[Corneal opacity]] is seen between two and four years of age and requires [[keratoplasty]] to restore sight. | ||
==== Ear ==== | ====Ear==== | ||
*[[Neurosensorial hearing loss]] | *[[Neurosensorial hearing loss]] | ||
| Line 76: | Line 76: | ||
*[[Enlarged tonsils]] and [[adenoids]] | *[[Enlarged tonsils]] and [[adenoids]] | ||
==== Heart ==== | ====Heart==== | ||
*[[Cardiomyopathy]] and [[valvular abnormalities]] | *[[Cardiomyopathy]] and [[valvular abnormalities]] | ||
==== Abdomen ==== | ====Abdomen==== | ||
*Organomegaly may be a manifestation. | *[[Organomegaly]] may be a manifestation. | ||
*Hernia may be a manifestation. | *[[Hernia]] may be a manifestation. | ||
=== Laboratory Findings === | ===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. | 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. | Management should be carried out by a multidisciplinary team and should include [[physiotherapy]] to maintain range of movement. | ||
===Medical Therapy=== | |||
=== Pharmacotherapy === | ===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. | 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 | ===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. | 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. | 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=== | ||
==Secondary Prevention=== | |||
==References== | ==References== | ||
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{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
[[Category: | [[Category:Endocrinology]] | ||
Latest revision as of 11:53, 22 July 2016
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
- 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.
Physical Examination
Appearence of the Patient
- Short stature
- Thoracic-lumbar kyphosis
Skin
- Hirsutism may be a manifestation.
Head
- Hydrocephaly can occur after the age of two.
Eyes
- Corneal opacity is seen between two and four years of age and requires keratoplasty to restore sight.
Ear
Nose
- Nasal secretion
Throat
Heart
Abdomen
- Organomegaly may be a manifestation.
- Hernia may be a manifestation.
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.