MPS1H/S
MCID: HRL004
MIFTS: 55

Hurler-Scheie Syndrome (MPS1H/S)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hurler-Scheie Syndrome

MalaCards integrated aliases for Hurler-Scheie Syndrome:

Name: Hurler-Scheie Syndrome 56 52 58 73 54 39 71
Mucopolysaccharidosis Ih/s 56 12 52 13 15
Mucopolysaccharidosis Type Ih/s 56 52 58 73
Mps1h/s 12 52 58 73
Mucopolysaccharidosis Type 1h/s 12 52 58
Mpsih/s 12 52 58
Alpha-L-Iduronidase Deficiency 73 71
Mucopolysaccharidosis I 43 71
Mps1-Hs 56 52
Mucopolysaccharidosis Type Ih/s; Mps1-Hs 56
Mucopolysaccharidosis 1h/s 73
Mps-Ih/s 73

Characteristics:

Orphanet epidemiological data:

58
hurler-scheie syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (United Kingdom),1-9/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: young Adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
alpha-l-iduronidase activity is <1% for all forms of mps1
mps1 types are distinguished clinically by age of onset and progression or by mutation(s)
onset of symptoms between ages 3-8 years of age
treatment with enzyme replacement therapy


HPO:

31
hurler-scheie syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare bone diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Hurler-Scheie Syndrome

NIH Rare Diseases : 52 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.

MalaCards based summary : Hurler-Scheie Syndrome, also known as mucopolysaccharidosis ih/s, is related to scheie syndrome and hurler syndrome, and has symptoms including joint stiffness and thick skin. An important gene associated with Hurler-Scheie Syndrome is IDUA (Alpha-L-Iduronidase), and among its related pathways/superpathways are Metabolism and Glycosaminoglycan metabolism. The drugs Immunoglobulins and Antibodies have been mentioned in the context of this disorder. Affiliated tissues include bone, tonsil and bone marrow, and related phenotypes are coarse facial features and splenomegaly

Disease Ontology : 12 A mucopolysaccharidosis I characterized by an intermediate severity of symptoms including short stature, corneal clouding, joint stiffening, umbilical hernia, dysostosis multiplex, hepatosplenomegaly, and little to no intellectual dysfunction that has material basis in homozygous or compound heterozygous mutation in IDUA on chromosome 4p16.3.

OMIM : 56 The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH; 607014), Scheie (MPS IS; 607016), and Hurler-Scheie (MPS IH/S) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972). Roubicek et al. (1985) presented 5 patients with alpha-L-iduronidase deficiency and a phenotype atypical for both Hurler and Scheie syndromes. They felt that the genetic compound explanation was acceptable for some cases, but that others must represent different mutations. (607015)

UniProtKB/Swiss-Prot : 73 Mucopolysaccharidosis 1H/S: A form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility.

Related Diseases for Hurler-Scheie Syndrome

Diseases related to Hurler-Scheie Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 103)
# Related Disease Score Top Affiliating Genes
1 scheie syndrome 32.1 SUMF1 SGSH NAGLU IDUA GALNS FUCA2
2 hurler syndrome 32.1 NAGLU IDUA GALNS FUCA2
3 mucopolysaccharidoses 30.8 NAGLU IDUA
4 mucolipidosis 29.9 SUMF1 GALNS
5 mucopolysaccharidosis-plus syndrome 29.4 SUMF1 SGSH NAGLU IDUA GALNS FUCA2
6 lysosomal storage disease 29.0 SUMF1 SGSH NAGLU IDUA GALNS
7 mucopolysaccharidosis, type ii 28.4 SUMF1 SGSH NAGLU IDUA GALNS
8 hypertelorism 10.3
9 otitis media 10.3
10 gaucher disease, type i 10.3
11 hydrocephalus, congenital, 1 10.3
12 yemenite deaf-blind hypopigmentation syndrome 10.3
13 hydrocephalus 10.3
14 mitral valve stenosis 10.3
15 gaucher's disease 10.3
16 craniosynostosis 10.3
17 heart valve disease 10.3
18 paraplegia 10.3
19 splenomegaly 10.3
20 lysosomal disease 10.3
21 nutritional deficiency disease 10.3
22 carpal tunnel syndrome 10.1
23 autosomal recessive disease 10.1
24 bone disease 10.1
25 dysostosis 10.1
26 lysosomal storage disease with skeletal involvement 10.1
27 odontoid hypoplasia 10.1
28 aortic disease 10.1
29 macroglossia 10.0
30 glycogen storage disease ii 10.0
31 fabry disease 10.0
32 scoliosis 10.0
33 urticaria 10.0
34 central nervous system disease 10.0
35 eye disease 10.0
36 nervous system disease 10.0
37 galactosialidosis 9.9 IDUA GALNS
38 glycoproteinosis 9.9 GALNS FUCA2
39 mongolian spot 9.9 NAGLU IDUA
40 mannosidosis, alpha b, lysosomal 9.9 IDUA FUCA2
41 gm1 gangliosidosis 9.9 IDUA GALNS
42 kluver-bucy syndrome 9.9 SGSH NAGLU
43 autoimmune disease 9.8
44 fish-eye disease 9.8
45 tangier disease 9.8
46 macular dystrophy, corneal 9.8
47 endocardial fibroelastosis 9.8
48 lecithin:cholesterol acyltransferase deficiency 9.8
49 3-methylglutaconic aciduria, type iii 9.8
50 retinitis pigmentosa 9.8

Graphical network of the top 20 diseases related to Hurler-Scheie Syndrome:



Diseases related to Hurler-Scheie Syndrome

Symptoms & Phenotypes for Hurler-Scheie Syndrome

Human phenotypes related to Hurler-Scheie Syndrome:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 coarse facial features 58 31 hallmark (90%) Very frequent (99-80%) HP:0000280
2 splenomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001744
3 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
4 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
5 corneal opacity 58 31 hallmark (90%) Very frequent (99-80%) HP:0007957
6 abnormal vertebral morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0003468
7 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
8 abnormal heart valve morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0001654
9 hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0100790
10 abnormality of the tonsils 58 31 hallmark (90%) Very frequent (99-80%) HP:0100765
11 limitation of joint mobility 58 31 hallmark (90%) Very frequent (99-80%) HP:0001376
12 rhinitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0012384
13 sensorineural hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000407
14 abnormal pyramidal sign 58 31 frequent (33%) Frequent (79-30%) HP:0007256
15 spinal canal stenosis 58 31 frequent (33%) Frequent (79-30%) HP:0003416
16 abnormal nerve conduction velocity 58 31 frequent (33%) Frequent (79-30%) HP:0040129
17 generalized hirsutism 58 31 occasional (7.5%) Occasional (29-5%) HP:0002230
18 cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001638
19 depressed nasal bridge 31 HP:0005280
20 scoliosis 31 HP:0002650
21 kyphosis 31 HP:0002808
22 recurrent respiratory infections 31 HP:0002205
23 joint stiffness 31 HP:0001387
24 umbilical hernia 31 HP:0001537
25 thick vermilion border 31 HP:0012471
26 dysostosis multiplex 31 HP:0000943
27 thickened skin 31 HP:0001072
28 pulmonary arterial hypertension 31 HP:0002092
29 micrognathia 31 HP:0000347
30 mitral regurgitation 31 HP:0001653
31 tracheal stenosis 31 HP:0002777
32 aortic regurgitation 31 HP:0001659
33 hirsutism 31 HP:0001007
34 obstructive sleep apnea 31 HP:0002870

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Skeletal Spine:
scoliosis
kyphosis
progressive lumbar gibbus

Skeletal:
joint stiffness
dysostosis multiplex

Growth Height:
short stature

Respiratory Airways:
tracheal stenosis

Skin Nails Hair Skin:
thick skin

Head And Neck Eyes:
corneal clouding

Head And Neck Mouth:
prominent lips

Respiratory Nasopharynx:
nasopharyngeal obstruction
hypertrophic tonsils

Neurologic Central Nervous System:
pachymeningitis cervicalis (cervical cord compression due to thickened dura)

Abdomen Liver:
hepatomegaly

Respiratory:
recurrent respiratory infections
obstructive sleep apnea

Abdomen External Features:
umbilical hernia

Head And Neck Face:
micrognathia

Skin Nails Hair Hair:
hirsutism

Head And Neck Nose:
low nasal bridge

Cardiovascular Heart:
mitral valve regurgitation
aortic valve regurgitation
dilated left atrium
dilated left ventricle
aortic valve thickening
more
Cardiovascular Vascular:
pulmonary hypertension, mild

Skeletal Limbs:
flat femurs with short metaphyses

Laboratory Abnormalities:
excretion of heparan sulfate in urine
excretion of dermatan sulfate in urine

Clinical features from OMIM:

607015

UMLS symptoms related to Hurler-Scheie Syndrome:


joint stiffness, thick skin

MGI Mouse Phenotypes related to Hurler-Scheie Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.8 GALNS IDUA NAGLU SERPIND1 SGSH SUMF1
2 craniofacial MP:0005382 9.56 IDUA NAGLU SGSH SUMF1
3 liver/biliary system MP:0005370 9.46 IDUA NAGLU SGSH SUMF1
4 renal/urinary system MP:0005367 9.35 GALNS IDUA NAGLU SERPIND1 SGSH
5 skeleton MP:0005390 9.1 GALNS HYAL4 IDUA NAGLU SGSH SUMF1

Drugs & Therapeutics for Hurler-Scheie Syndrome

Drugs for Hurler-Scheie Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 59)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunoglobulins Phase 4
2 Antibodies Phase 4
3
Clotrimazole Approved, Vet_approved Phase 1, Phase 2 23593-75-1 2812
4
Miconazole Approved, Investigational, Vet_approved Phase 1, Phase 2 22916-47-8 4189
5
Azathioprine Approved Phase 1, Phase 2 446-86-6 2265
6
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 6741
7
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
8
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5
9 Prednisolone acetate Approved, Vet_approved Phase 2 52-21-1
10
Prednisolone Approved, Vet_approved Phase 2 50-24-8 5755
11
Mycophenolic acid Approved Phase 2 24280-93-1 446541
12
tannic acid Approved Phase 2 1401-55-4
13
Mesna Approved, Investigational Phase 2 3375-50-6 598
14
Benzocaine Approved, Investigational Phase 2 94-09-7, 1994-09-7 2337
15
Adalimumab Approved Phase 1, Phase 2 331731-18-1 16219006
16
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
17
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
18
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
19
rituximab Approved Phase 2 174722-31-7 10201696
20
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986
21
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
22
Zinc Approved, Investigational Phase 1, Phase 2 7440-66-6 32051
23
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
24
Busulfan Approved, Investigational Phase 2 55-98-1 2478
25
alemtuzumab Approved, Investigational Phase 2 216503-57-0
26
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
27
Prednisolone hemisuccinate Experimental Phase 2 2920-86-7
28 Tocotrienol Investigational Phase 2 6829-55-6
29 Anti-Infective Agents Phase 1, Phase 2
30 Cyclosporins Phase 1, Phase 2
31 Antifungal Agents Phase 1, Phase 2
32 Calcineurin Inhibitors Phase 1, Phase 2
33 Dermatologic Agents Phase 1, Phase 2
34 Antimetabolites Phase 1, Phase 2
35 Insulin, Globin Zinc Phase 1, Phase 2
36 insulin Phase 1, Phase 2
37 Antibodies, Monoclonal Phase 1, Phase 2
38 Methylprednisolone Acetate Phase 2
39 Antitubercular Agents Phase 2
40 Anti-Bacterial Agents Phase 2
41 Antibiotics, Antitubercular Phase 2
42 Pharmaceutical Solutions Phase 1, Phase 2
43 Anti-Inflammatory Agents Phase 1, Phase 2
44 Thymoglobulin Phase 1, Phase 2
45 Antilymphocyte Serum Phase 2
46 Alpha-lipoic Acid Phase 2
47 Vitamins Phase 2
48 Thioctic Acid Phase 2
49 Tocopherols Phase 2
50 Tocotrienols Phase 2

Interventional clinical trials:

(show top 50) (show all 51)
# Name Status NCT ID Phase Drugs
1 A Multicenter, Multinational, Open-Label Study of the Effects of Aldurazyme (Laronidase) Treatment on Lactation in Women With Mucopolysaccharidosis I (MPS I) and Their Breastfed Infants Unknown status NCT00418821 Phase 4
2 A Multicenter, Multinational, Randomized, Dose-Optimization Study of the Safety and Pharmacodynamic Response of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I Completed NCT00144781 Phase 4
3 A Multicenter, Multinational, Open-Label Study of Anti-Laronidase Antibody Formation and Urinary GAG Levels in Patients With Mucopolysaccharidosis I (MPS I) Being Treated With Aldurazyme® (Laronidase). Completed NCT00144768 Phase 4 laronidase
4 A Multicenter, Multinational, Open-Label Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Patients With Mucopolysaccharidosis I Completed NCT00146770 Phase 3
5 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Multinational, Clinical Study of Recombinant Human Alpha L-Iduronidase In Patients With Mucopolysaccharidosis I Completed NCT00912925 Phase 3
6 A Safety Confirmatory Study of JC0498 (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients Completed NCT00258011 Phase 3
7 A Phase III Trial of ALD-101 Adjuvant Therapy of Unrelated Umbilical Cord Blood Transplantation (UCBT) in Patients With Inborn Errors of Metabolism Terminated NCT00654433 Phase 3
8 Phase II/III, Randomized, Clinical Trial of the Effects of Nutropin AQ® on Growth and Bone Metabolism in Children With MPS I, II, and VI and Short Stature Terminated NCT00748969 Phase 2, Phase 3 Somatropin (DNA origin)
9 A Phase II Open-Label Clinical Trial of Recombinant Human Alpha-L-iduronidase (Aldurazyme®) to Evaluate the Safety and Pharmacokinetics in Mucopolysaccharidosis I (MPS I) Patients Less Than 5 Years Old Completed NCT00146757 Phase 2
10 A Trial of Antigen-specific Immune Tolerance Induction in Mucopolysaccharidosis I (MPS I) Patients Initiating Enzyme Replacement Therapy With Aldurazyme® (Laronidase) Completed NCT00741338 Phase 1, Phase 2 Cyclosporine A (CsA);Azathioprine (Aza)
11 An Extension Study Evaluating Long Term Safety and Activity of AGT-181 in Patients With Mucopolysaccharidosis I Who Were Previously Enrolled in Studies With AGT-181 Completed NCT03071341 Phase 1, Phase 2 AGT-181
12 Phase II Study of Combined Laronidase (AldurazymeTM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH) Completed NCT00176891 Phase 2 Laronidase ERT
13 Hematopoietic Stem Cell Transplantation for Hurler Syndrome, Maroteaux Lamy Syndrome (MPS VI), and Alpha Mannosidase Deficiency (Mannosidosis) Completed NCT00176917 Phase 2 Busulfan, Cyclophosphamide, ATG
14 A Two-Stage, Phase 1/2, Open-Label Study of the Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome) Completed NCT03053089 Phase 1, Phase 2 AGT-181
15 Allogeneic Hematopoietic Stem Cell Transplantation for Standard Risk Inherited Metabolic Disorders Completed NCT01043640 Phase 2 Campath-1H;Cyclophosphamide;Busulfan;Cyclosporine A;Mycophenolate Mofetil
16 Phase I/II Trial Of Hematopoietic Stem Cell Transplant (HSCT) For Children With A Genetic Disease Of Blood Cells Without An HLA-Matched Sibling Donor Completed NCT00730314 Phase 1, Phase 2
17 Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI Completed NCT02437253 Phase 1, Phase 2 Adalimumab
18 Phase 1/2 Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I and II Recruiting NCT03153319 Phase 1, Phase 2 Adalimumab Injection [Humira];Saline Solution for Injection
19 MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
20 Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem and Progenitor Cells Genetically Modified With IDUA Lentiviral Vector Encoding for the Human α-L-iduronidase Gene for the Treatment of Patients Affected by Mucopolysaccharidosis Type I, Hurler Variant Recruiting NCT03488394 Phase 1, Phase 2
21 A Phase I/II Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Intracisternal RGX-111 in Subjects With Mucopolysaccharidosis Type I Recruiting NCT03580083 Phase 1, Phase 2
22 PEDS024, Phase I/II Feasibility Study of Busulfan Fludarabine and Thiotepa Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation (HSCT) for Children With Non-Malignant Disorders Recruiting NCT03513328 Phase 1, Phase 2 Thiotepa--single daily dose;Thiotepa--escalated dose
23 A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I) Active, not recruiting NCT02702115 Phase 1, Phase 2
24 Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders Active, not recruiting NCT01372228 Phase 1, Phase 2
25 Phase I/II Study of JR‐171 ㏌ Patients With Mucopolysaccharidosis Type I Not yet recruiting NCT04227600 Phase 1, Phase 2 JR-171
26 Sleeping Beauty Transposon-Engineered Plasmablasts for Expression and Delivery of Alpha-L-iduronidase in Patients With Hurler Syndrome That Have Previously Undergone Allogeneic Transplantation Not yet recruiting NCT04284254 Phase 1, Phase 2 Autologous Plasmablasts
27 Treatment of Lysosomal and Peroxisomal Inborn Errors of Metabolism by Hematopoietic Cell Transplantation Terminated NCT00668564 Phase 2 Cyclophosphamide;Campath-1H;Busulfan
28 A Phase 1 Safety and Dose-Finding Study of a Human Insulin Receptor Monoclonal Antibody-Human Alpha-L-iduronidase (HIRMAb-IDUA) Fusion Protein, AGT-181 in Adult Patients With Mucopolysaccharidosis I (MPS I, Hurler Syndrome) Unknown status NCT02371226 Phase 1 AGT-181 (HIRMAb-IDUA)
29 An Extension Study of AGT-181-102 Evaluating Safety and Glycosaminoglycans (GAGs) in Adult Patients With Hurler-Scheie or Scheie Syndrome Who Have Completed 8-Weeks of Dosing With AGT-181 in Study AGT-181-102 Completed NCT02597114 Phase 1 AGT-181
30 Pilot Study of Administration of Intravenous Laronidase Following Allogeneic Transplantation for Hurler Syndrome Completed NCT01173016 Phase 1 Laronidase
31 Intrathecal Enzyme Replacement Therapy For Patients With Mucopolysaccharidosis Type I (Hurler Syndrome) Completed NCT00638547 Phase 1 IRT Laronidase
32 Abatacept for Post-Transplant Immune Suppression in Children and Adolescents Receiving Allogeneic Hematopoietic Stem Cell Transplants for Non-Malignant Diseases Completed NCT01917708 Phase 1 Abatacept
33 A Single-Arm Study to Assess the Safety of Transplantation With Human Placental-Derived Stem-Cells Combined With Unrelated and Related Cord Blood in Subjects With Certain Malignant Hematologic Diseases and Non-Malignant Disorders Active, not recruiting NCT01586455 Phase 1 Human Placental Derived Stem Cell
34 An Extension Study of Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis I Terminated NCT00786968 Phase 1 laronidase
35 A Study of Intrathecal Enzyme Replacement Therapy for Spinal Cord Compression in Mucopolysaccharidosis I Terminated NCT00215527 Phase 1 laronidase
36 Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Unknown status NCT00005900
37 Longitudinal Studies of Brain Structure and Function in MPS Disorders Completed NCT01870375
38 Lysosomal Storage Disease: Health, Development, and Functional Outcome Surveillance in Preschool Children Completed NCT01938014
39 Behavioral Challenges in Children With Mucopolysaccharidosis Type I-III and Parental Coping Strategies Completed NCT03161171
40 Magnetic Resonance Spectroscopy (MRS) to Determine Neuroinflammation and Oxidative Stress in MPS I Completed NCT03576729
41 A Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I Completed NCT00852358 laronidase
42 Characterizing the Neurobehavioral Phenotype(s) in MPS III Completed NCT01873911
43 Mucopolysaccharidosis I (MPS I) Registry Recruiting NCT00144794
44 Long Term Follow Up Of Patients Who Have Received Gene Therapy Or Gene Marked Products at St. Jude Children's Research Hospital Recruiting NCT00695279
45 Biomarker for Hurler Disease - An International, Multicenter, Epidemiological Protocol Active, not recruiting NCT02298712
46 An Extension Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I Enrolling by invitation NCT02232477 Intrathecal recombinant human alpha iduronidase
47 Expanded Access Protocol for CaspaCIDe T Cells From An HLA-Partially Matched Related Donor After Negative Selection of TCR αβ+T Cells In Pediatric Patients Affected by Hematological and Other Disorders No longer available NCT03639844 rimiducid
48 Unrecognized Mucopolysaccharidosis I, II, IVA, and VI in the Pediatric Rheumatology Population Terminated NCT01675674
49 MT2011-21C Laronidase (Aldurazyme TM) Enzyme Replacement Therapy (ERT) With Hematopoietic Stem Cell Transplantation (HSCT) for Hurler Syndrome (MPS IH). Terminated NCT01572636 Laronidase
50 Mucopolysaccharidosis (MPS) I, II, and VI Screening in a High Risk Population With Previous Surgical Repair or Presence of Inguinal and/or Umbilical Hernia in Combination With Pediatric Ear, Nose and Throat (ENT) Surgery (Adenoidectomy and/or Tonsillectomy and/or Tympanostomy) (The HATT Project) Terminated NCT02095015

Search NIH Clinical Center for Hurler-Scheie Syndrome

Inferred drug relations via UMLS 71 / NDF-RT 50 :


Laronidase

Cochrane evidence based reviews: mucopolysaccharidosis i

Genetic Tests for Hurler-Scheie Syndrome

Anatomical Context for Hurler-Scheie Syndrome

MalaCards organs/tissues related to Hurler-Scheie Syndrome:

40
Bone, Tonsil, Bone Marrow, Lung, Testes, Spinal Cord, Skin

Publications for Hurler-Scheie Syndrome

Articles related to Hurler-Scheie Syndrome:

(show top 50) (show all 96)
# Title Authors PMID Year
1
Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity. 61 54 56 6
10466419 1999
2
Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families. 61 56 6
9391892 1997
3
Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations. 6 56
8664897 1996
4
Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S). 54 61 6
7550232 1995
5
Mucopolysaccharidosis Type I 6 61
20301341 2002
6
Grouped papules in Hurler-Scheie syndrome. 61 56
8912609 1996
7
Radiological findings in patients with mucopolysaccharidosis I H/S (Hurler-Scheie syndrome). 61 56
3114705 1987
8
Postmortem findings in the Hurler-Scheie syndrome (mucopolysaccharidosis I-H/S). 56 61
6814547 1982
9
Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals. 56
21502868 2011
10
Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II. 56
19748810 2009
11
Mutational analysis of the alpha-L-iduronidase gene in 10 unrelated Korean type I mucopolysaccharidosis patients: Identification of four novel mutations. 6
15521993 2004
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Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. 56
11735025 2001
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Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S. 6
10735634 2000
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Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene. 56
7550242 1995
15
Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes. 6
8213840 1993
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Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area. 6
8328452 1993
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Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3. 56
2220820 1990
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Respiratory complications of mucopolysaccharide storage disorders. 56
3134589 1988
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Mucopolysaccharidosis type I subtypes. Presence of immunologically cross-reactive material and in vitro enhancement of the residual alpha-L-iduronidase activities. 56
3121676 1988
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Echocardiographic abnormalities in the mucopolysaccharide storage diseases. 56
3122547 1988
21
Airway obstruction and sleep apnea in Hurler and Hunter syndromes. 56
3931528 1985
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[Psychotic symptoms during the evolution of dementia in muco- polysaccharidosis of Hurler-Scheie phenotype]. 56
3935090 1985
23
The clinical spectrum of alpha-L-iduronidase deficiency. 56
3922223 1985
24
Properties of alpha-L-iduronidase in cultured skin fibroblasts from alpha-L-iduronidase-deficient patients. 56
6421718 1984
25
Hurler-Scheie phenotype: a report of two pairs of inbred sibs. 56
119701 1979
26
Hurler/Scheie phenotype. Report of an inbred sibship with tapeto-retinal degeneration and electron-microscopie examination of the conjuctiva. 56
96404 1978
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alpha-L-iduronidase deficiency and possible Hurler-Scheie genetic compound. Clinical, pathologic, and biochemical findings. 56
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Allelism, non-allelism, and genetic compounds among the mucopolysaccharidoses. 56
4112371 1972
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Laronidase treatment of mucopolysaccharidosis I. 61 54
15691212 2005
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The alpha-L-iduronidase mutations R89Q and R89W result in an attenuated mucopolysaccharidosis type I clinical presentation. 54 61
14559116 2003
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Orofacial features of Scheie (Hurler-Scheie) syndrome (alpha-L-iduronidase deficiency). 54 61
2115154 1990
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Anterior segment optical coherence tomography and in vivo confocal microscopy in cases of mucopolysaccharidosis. 61
32405572 2020
33
Implementation of an Affordable Method for MPS Diagnosis from Urine Screening to Enzymatic Confirmation: Results of a Pilot Study in Morocco. 61
32162878 2020
34
Identification of a novel compound heterozygous IDUA mutation underlies Mucopolysaccharidoses type I in a Chinese pedigree. 61
31758674 2020
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A longitudinal study of neurocognition and behavior in patients with Hurler-Scheie syndrome heterozygous for the L238Q mutation. 61
31304092 2019
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Mutation Analysis of the IDUA Gene in Iranian Patients with Mucopolysaccharidosis Type 1: Identification of Four Novel Mutations. 61
31298590 2019
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Enzyme replacement therapy with laronidase (Aldurazyme®) for treating mucopolysaccharidosis type I. 61
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Hurler-Scheie syndrome in Niger: a case series. 61
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Markedly Elevated Intracranial Pressure Treated With Cranial Vault Expansion, Instead of CSF Shunting, in a Child With Hurler-Scheie Syndrome and Multiple Suture Craniosynostosis. 61
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Deep Anterior Lamellar Keratoplasty in a Case of Hurler-Scheie Syndrome Undergoing Enzyme Replacement Therapy. 61
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p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS-7 cells. 61
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Novel splice site IDUA gene mutation in Tunisian pedigrees with hurler syndrome. 61
29843745 2018
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P-Tau and Subunit c Mitochondrial ATP Synthase Accumulation in the Central Nervous System of a Woman with Hurler-Scheie Syndrome Treated with Enzyme Replacement Therapy for 12 Years. 61
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Adeno-associated viral gene therapy for mucopolysaccharidoses exhibiting neurodegeneration. 61
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Clinical features of Mexican patients with Mucopolysaccharidosis type I. 61
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Mucopolysaccharidoses - Clinical Spectrum and Frequency of Different Types. 61
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Mucopolysaccharidoses Causing Valvular Heart Disease: Report and Review of Surgical Management. 61
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Identification and characterization of 20 novel pathogenic variants in 60 unrelated Indian patients with mucopolysaccharidoses type I and type II. 61
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Enzyme replacement therapy with laronidase (Aldurazyme(®)) for treating mucopolysaccharidosis type I. 61
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Variations for Hurler-Scheie Syndrome

ClinVar genetic disease variations for Hurler-Scheie Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IDUA NM_000203.5(IDUA):c.1205G>A (p.Trp402Ter)SNV Pathogenic 11908 rs121965019 4:996535-996535 4:1002747-1002747
2 IDUA , SLC26A1 NM_000203.5(IDUA):c.208C>T (p.Gln70Ter)SNV Pathogenic 11909 rs121965020 4:981646-981646 4:987858-987858
3 IDUA NM_000203.5(IDUA):c.1598C>G (p.Pro533Arg)SNV Pathogenic 11910 rs121965021 4:997206-997206 4:1003418-1003418
4 IDUA NM_000203.5(IDUA):c.1469T>C (p.Leu490Pro)SNV Pathogenic 11919 rs121965027 4:996890-996890 4:1003102-1003102
5 IDUA NM_000203.4(IDUA):c.1960T>G (p.Ter654Gly)SNV Pathogenic 11920 rs387906504 4:998179-998179 4:1004391-1004391
6 IDUA NM_000203.5(IDUA):c.266G>A (p.Arg89Gln)SNV Pathogenic 11922 rs121965029 4:981704-981704 4:987916-987916
7 IDUA NM_000203.5(IDUA):c.1091C>T (p.Thr364Met)SNV Pathogenic 11925 rs121965032 4:996175-996175 4:1002387-1002387
8 IDUA NM_000203.5(IDUA):c.1037T>G (p.Leu346Arg)SNV Pathogenic 11927 rs121965033 4:996121-996121 4:1002333-1002333
9 IDUA NM_000203.5(IDUA):c.300-3C>GSNV Conflicting interpretations of pathogenicity 551563 rs1226056948 4:994397-994397 4:1000609-1000609
10 IDUA NM_000203.5(IDUA):c.1855C>G (p.Arg619Gly)SNV Uncertain significance 11924 rs121965031 4:998074-998074 4:1004286-1004286

UniProtKB/Swiss-Prot genetic disease variations for Hurler-Scheie Syndrome:

73 (show all 25)
# Symbol AA change Variation ID SNP ID
1 IDUA p.His82Pro VAR_003353 rs794727239
2 IDUA p.Gln380Arg VAR_003366 rs762903007
3 IDUA p.Leu490Pro VAR_003374 rs121965027
4 IDUA p.Pro496Leu VAR_003376 rs772416503
5 IDUA p.Met504Thr VAR_003377
6 IDUA p.Pro533Arg VAR_003378 rs121965021
7 IDUA p.Trp626Arg VAR_003379 rs128147554
8 IDUA p.Leu346Arg VAR_017436 rs121965033
9 IDUA p.Arg619Gly VAR_017437 rs121965031
10 IDUA p.Ala79Val VAR_020975 rs747981483
11 IDUA p.Leu238Gln VAR_020980 rs148789453
12 IDUA p.Ser260Phe VAR_020981
13 IDUA p.Arg363Cys VAR_020984 rs750496798
14 IDUA p.Ser423Arg VAR_020985 rs931627770
15 IDUA p.Phe602Ile VAR_020986
16 IDUA p.Arg628Pro VAR_020987 rs200448421
17 IDUA p.Gly84Arg VAR_066216
18 IDUA p.Glu178Lys VAR_066218 rs992336192
19 IDUA p.Phe188Leu VAR_066219
20 IDUA p.Gly265Arg VAR_066221 rs369090960
21 IDUA p.Glu276Lys VAR_066222
22 IDUA p.Leu396Pro VAR_066226
23 IDUA p.Ala436Pro VAR_066227
24 IDUA p.Pro496Arg VAR_066229 rs772416503
25 IDUA p.Leu535Phe VAR_066230

Expression for Hurler-Scheie Syndrome

Search GEO for disease gene expression data for Hurler-Scheie Syndrome.

Pathways for Hurler-Scheie Syndrome

Pathways related to Hurler-Scheie Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.39 SUMF1 SGSH NAGLU IDUA HYAL4 GALNS
2
Show member pathways
12.25 SGSH NAGLU IDUA
3
Show member pathways
11.84 SGSH NAGLU IDUA
4 11.27 SUMF1 SGSH NAGLU IDUA HYAL4 GALNS
5
Show member pathways
10.65 SGSH NAGLU IDUA HYAL4 GALNS

GO Terms for Hurler-Scheie Syndrome

Cellular components related to Hurler-Scheie Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.63 SGSH SERPIND1 NAGLU IDUA GALNS FUCA2
2 endoplasmic reticulum lumen GO:0005788 9.43 SUMF1 SERPIND1 FUCA2
3 lysosome GO:0005764 9.35 SGSH NAGLU IDUA GALNS FUCA2
4 azurophil granule lumen GO:0035578 9.32 GALNS FUCA2
5 lysosomal lumen GO:0043202 8.92 SGSH NAGLU IDUA GALNS

Biological processes related to Hurler-Scheie Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.5 SUMF1 SERPIND1 FUCA2
2 carbohydrate metabolic process GO:0005975 9.43 IDUA HYAL4 FUCA2
3 metabolic process GO:0008152 9.26 NAGLU IDUA HYAL4 FUCA2
4 chondroitin sulfate catabolic process GO:0030207 9.16 IDUA HYAL4
5 glycosaminoglycan catabolic process GO:0006027 8.92 SGSH NAGLU IDUA HYAL4

Molecular functions related to Hurler-Scheie Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.43 SGSH HYAL4 GALNS
2 hydrolase activity GO:0016787 9.43 SGSH NAGLU IDUA HYAL4 GALNS FUCA2
3 sulfuric ester hydrolase activity GO:0008484 9.16 SGSH GALNS
4 hydrolase activity, acting on glycosyl bonds GO:0016798 8.92 NAGLU IDUA HYAL4 FUCA2

Sources for Hurler-Scheie Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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