Hurler-Scheie syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: MPS1H/S
MPS1-HS
Mucopolysaccharidosis type IH/S
Mucopolysaccharidosis type 1H/S
Number of Symptoms 181
OrphanetNr: 93476
OMIM Id: 607015
ICD-10: E76.0
UMLs: C0086431
MeSH:
MedDRA:
Snomed: 26745009

Prevalence, inheritance and age of onset:

Prevalence: 0.24 of 100 000 - PMID: 18796143 [IBIS]
Inheritance: Autosomal recessive
- PMID: 813180 [IBIS]
Age of onset: Childhood
- PMID: 24675674 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Lysosomal disease with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Mucopolysaccharidosis type 1
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare eye disease
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Mucopolysaccharidosis type I (MPS I) is a panethnic, chronic and progressive, autosomal recessive lysosomal storage disease in which degradation of the glycoaminoglycans (GAGs) dermatan and heparan sulphate is deficient. Currently three clinical syndromes are often referred to which, from severe through intermediate to mild phenotypes, are termed Hurler, Hurler-Scheie and Scheie. It is clear however that this is an oversimplification and that the full phenotypic spectrum of disease forms a continuum (PMID:18796143).

Symptom Information: Sort by abundance 

1
 (HPO:0002091) Restrictive ventilatory defect 19117856 IBIS 46 / 7739
2
 (HPO:0001538) Protuberant abdomen 119701; 11131359 IBIS 36 / 7739
3
 (HPO:0002027) Abdominal pain 19117856 IBIS 184 / 7739
4
 (HPO:0002019) Constipation 19117856 IBIS 194 / 7739
5
 (HPO:0002014) Diarrhea 19117856; 3922223 IBIS 225 / 7739
6
 (HPO:0000316) Hypertelorism 2512446 IBIS 644 / 7739
7
 (HPO:0000520) Proptosis 6433708 IBIS 192 / 7739
8
 (HPO:0000481) Abnormality of the cornea Very frequent [Orphanet] 19117856; 2512446 IBIS 124 / 7739
9
 (HPO:0007759) Opacification of the corneal stroma 6433708 IBIS 77 / 7739
10
 (HPO:0000531) Corneal crystals 23917744 IBIS 9 / 7739
11
 (HPO:0000483) Astigmatism 6433708 IBIS 67 / 7739
12
 (HPO:0007957) Corneal opacity Frequent [IBIS] 24675674; 19117856; 811694; 813180; 119701; 3922223; 6433708; 11131359 IBIS 84 / 7739
13
 (HPO:0007807) Optic nerve compression 19117856 IBIS 6 / 7739
14
 (HPO:0001085) Papilledema 23917744 IBIS 31 / 7739
15
 (HPO:0007703) Abnormality of retinal pigmentation 119701 IBIS 21 / 7739
16
 (HPO:0000546) Retinal degeneration 19117856 IBIS 61 / 7739
17
 (HPO:0000540) Hypermetropia 6433708 IBIS 99 / 7739
18
 (HPO:0000662) Nyctalopia 19117856; 119701 IBIS 92 / 7739
19
 (HPO:0007994) Peripheral visual field loss 19117856 IBIS 13 / 7739
20
 (HPO:0000505) Visual impairment 2512446 IBIS 297 / 7739
21
 (HPO:0000529) Progressive visual loss 19117856 IBIS 54 / 7739
22
 (HPO:0000501) Glaucoma Rare [IBIS] 24675674; 19117856 IBIS 180 / 7739
23
 (HPO:0000498) Blepharitis 3922223 IBIS 27 / 7739
24
 (HPO:0002099) Asthma Occasional [IBIS] 24675674; 19117856 IBIS 62 / 7739
25
 (HPO:0002093) Respiratory insufficiency 19117856 IBIS 410 / 7739
26
 (HPO:0002875) Exertional dyspnea 2512446 IBIS 29 / 7739
27
 (HPO:0002205) Recurrent respiratory infections 119701; 2512446; 3922223 IBIS 254 / 7739
28
 (HPO:0011109) Chronic sinusitis 19117856 IBIS 17 / 7739
29
 (HPO:0002777) Tracheal stenosis 19117856 IBIS 35 / 7739
30
 (HPO:0004322) Short stature Very frequent [Orphanet] 19117856; 813180; 119701; 2512446; 3922223 IBIS 1232 / 7739
31
 (HPO:0003510) Severe short stature 811694; 119701; 11131359 IBIS 90 / 7739
32
 (HPO:0011020) Abnormality of mucopolysaccharide metabolism 22074387; 119701 IBIS 17 / 7739
33
 (HPO:0008301) Dermatan sulfate excretion in urine 813180; 119701; 2512446; 3922223 IBIS 8 / 7739
34
 (HPO:0002159) Heparan sulfate excretion in urine 813180; 3922223; 6433708 IBIS 12 / 7739
35
 (HPO:0004371) Abnormality of glycosaminoglycan metabolism 19117856 IBIS 3 / 7739
36
 (HPO:0003541) Urinary glycosaminoglycan excretion 19117856; 811694 IBIS 6 / 7739
37
 (HPO:0001640) Cardiomegaly 811694 IBIS 81 / 7739
38
 (HPO:0001648) Cor pulmonale Rare [IBIS] 24675674 IBIS 16 / 7739
39
 (HPO:0004382) Mitral valve calcification 811694 IBIS 5 / 7739
40
 (HPO:0001654) Abnormality of the heart valves Frequent [IBIS] Very frequent [Orphanet] 24675674 IBIS 49 / 7739
41
 (HPO:0004380) Aortic valve calcification 811694 IBIS 5 / 7739
42
 (HPO:0001650) Aortic valve stenosis 2512446 IBIS 49 / 7739
43
 (HPO:0001638) Cardiomyopathy Occasional [IBIS] Occasional [Orphanet] 24675674 IBIS 192 / 7739
44
 (HPO:0007082) Dilated third ventricle 2512446 IBIS 3 / 7739
45
 (HPO:0006956) Dilation of lateral ventricles 2512446 IBIS 13 / 7739
46
 (HPO:0001635) Congestive heart failure Rare [IBIS] 24675674; 811694 IBIS 232 / 7739
47
 (HPO:0004356) Abnormality of lysosomal metabolism 22074387 IBIS 6 / 7739
48
 (HPO:0012398) Peripheral edema 811694 IBIS 12 / 7739
49
 (HPO:0000403) Recurrent otitis media 23917744; 6433708 IBIS 61 / 7739
50
 (HPO:0000158) Macroglossia Frequent [IBIS] 24675674; 19117856; 3922223; 11131359 IBIS 119 / 7739
51
 (HPO:0003388) Easy fatigability 2512446 IBIS 34 / 7739
52
 (HPO:0008967) Exercise-induced muscle stiffness 2512446 IBIS 6 / 7739
53
 (HPO:0003690) Limb muscle weakness 119701 IBIS 41 / 7739
54
 (HPO:0007340) Lower limb muscle weakness 19117856 IBIS 61 / 7739
55
 (MedDRA:10007697) Carpal tunnel syndrome Occasional [IBIS] 24675674 IBIS 16 / 7739
56
 (HPO:0006801) Hyperactive deep tendon reflexes 11131359 IBIS 21 / 7739
57
 (HPO:0002061) Lower limb spasticity 2512446 IBIS 56 / 7739
58
 (HPO:0001263) Global developmental delay 3922223 IBIS 853 / 7739
59
 (HPO:0001249) Intellectual disability 3922223 IBIS 1089 / 7739
60
 (HPO:0001256) Intellectual disability, mild 813180 IBIS 141 / 7739
61
 (HPO:0001270) Motor delay 3922223 IBIS 322 / 7739
62
 (HPO:0002360) Sleep disturbance Frequent [IBIS] 24675674 IBIS 113 / 7739
63
 (HPO:0002870) Obstructive sleep apnea 19117856 IBIS 16 / 7739
64
 (HPO:0100543) Cognitive impairment Occasional [IBIS] 24675674 IBIS 230 / 7739
65
 (HPO:0002516) Increased intracranial pressure 23917744 IBIS 47 / 7739
66
 (HPO:0001288) Gait disturbance 19117856; 119701 IBIS 318 / 7739
67
 (HPO:0002315) Headache 19117856 IBIS 175 / 7739
68
 (HPO:0002857) Genu valgum Occasional [IBIS] 24675674; 19117856; 2512446 IBIS 144 / 7739
69
 (HPO:0006499) Abnormality of femoral epiphysis 2512446 IBIS 3 / 7739
70
 (HPO:0003891) Abnormality of the humeral epiphysis 2512446 IBIS 1 / 7739
71
 (HPO:0100490) Camptodactyly of finger 119701 IBIS 212 / 7739
72
 (HPO:0002673) Coxa valga 119701 IBIS 57 / 7739
73
 (HPO:0001761) Pes cavus Occasional [IBIS] 24675674 IBIS 225 / 7739
74
 (HPO:0003170) Abnormality of the acetabulum 2512446 IBIS 3 / 7739
75
 (HPO:0001374) Congenital hip dislocation 2512446 IBIS 51 / 7739
76
 (HPO:0002869) Flared iliac wings 119701; 2512446 IBIS 20 / 7739
77
 (HPO:0002866) Hypoplastic iliac wing 119701 IBIS 34 / 7739
78
 (HPO:0001385) Hip dysplasia Occasional [IBIS] 24675674; 19117856 IBIS 242 / 7739
79
 (HPO:0006380) Knee flexion contracture 811694; 11131359 IBIS 56 / 7739
80
 (HPO:0005089) Abnormal metaphyseal trabeculation 6433708 IBIS 3 / 7739
81
 (HPO:0002818) Abnormality of the radius 119701 IBIS 96 / 7739
82
 (HPO:0002997) Abnormality of the ulna 119701; 6433708 IBIS 75 / 7739
83
 (HPO:0004035) Abnormality of the styloid process of ulna 6433708 IBIS 1 / 7739
84
 (HPO:0001498) Carpal bone hypoplasia 119701 IBIS 17 / 7739
85
 (HPO:0001163) Abnormality of the metacarpal bones 6433708 IBIS 149 / 7739
86
 (HPO:0001248) Short tubular bones of the hand 119701 IBIS 4 / 7739
87
 (HPO:0002987) Elbow flexion contracture 11131359 IBIS 64 / 7739
88
 (HPO:0011912) Abnormality of the glenoid fossa 2512446 IBIS 1 / 7739
89
 (HPO:0006467) Limited shoulder movement 2512446 IBIS 3 / 7739
90
 (HPO:0000347) Micrognathia 6433708 IBIS 426 / 7739
91
 (HPO:0000278) Retrognathia 2512446 IBIS 100 / 7739
92
 (HPO:0000268) Dolichocephaly 23917744; 6433708 IBIS 144 / 7739
93
 (HPO:0011329) Abnormality of cranial sutures 6433708 IBIS 1 / 7739
94
 (HPO:0010537) Wide cranial sutures 23917744; 3922223 IBIS 21 / 7739
95
 (HPO:0005442) Widely patent coronal suture 23917744 IBIS 3 / 7739
96
 (HPO:0002679) Abnormality of the sella turcica 119701 IBIS 1 / 7739
97
 (HPO:0002680) J-shaped sella turcica 6433708 IBIS 15 / 7739
98
 (HPO:0002693) Abnormality of the skull base 3922223 IBIS 2 / 7739
99
 (HPO:0001363) Craniosynostosis 23917744 IBIS 132 / 7739
100
 (HPO:0004442) Sagittal craniosynostosis 23917744 IBIS 16 / 7739
101
 (HPO:0000256) Macrocephaly 23917744; 6433708 IBIS 298 / 7739
102
 (HPO:0002691) Platybasia 2512446 IBIS 10 / 7739
103
 (HPO:0000772) Abnormality of the ribs 2512446 IBIS 146 / 7739
104
 (HPO:0000885) Broad ribs 6433708 IBIS 21 / 7739
105
 (HPO:0000900) Thickened ribs 119701 IBIS 9 / 7739
106
 (HPO:0006584) Small abnormally formed scapulae 119701 IBIS 4 / 7739
107
 (HPO:0000768) Pectus carinatum 11131359 IBIS 136 / 7739
108
 (HPO:0000914) Shield chest 3922223 IBIS 14 / 7739
109
 (HPO:0000773) Short ribs 3922223 IBIS 70 / 7739
110
 (HPO:0003312) Abnormal form of the vertebral bodies Very frequent [Orphanet] 119701; 3922223 IBIS 172 / 7739
111
 (HPO:0004580) Anterior scalloping of vertebral bodies 2512446 IBIS 2 / 7739
112
 (HPO:0005121) Posterior scalloping of vertebral bodies 2512446 IBIS 4 / 7739
113
 (HPO:0000926) Platyspondyly 6433708 IBIS 150 / 7739
114
 (HPO:0000470) Short neck 2512446; 3922223; 6433708 IBIS 345 / 7739
115
 (HPO:0100712) Abnormality of the lumbar spine 119701; 2512446; 3922223 IBIS 1 / 7739
116
 (HPO:0003418) Back pain 19117856 IBIS 17 / 7739
117
 (HPO:0002808) Kyphosis Frequent [IBIS] 24675674; 19117856 IBIS 289 / 7739
118
 (HPO:0002751) Kyphoscoliosis 19117856; 811694; 11131359 IBIS 131 / 7739
119
 (HPO:0002938) Lumbar hyperlordosis 2512446 IBIS 73 / 7739
120
 (HPO:0002650) Scoliosis Occasional [IBIS] 24675674; 19117856 IBIS 705 / 7739
121
 (HPO:0008462) Cervical instability 19117856 IBIS 4 / 7739
122
 (HPO:0000938) Osteopenia 19117856 IBIS 138 / 7739
123
 (HPO:0002829) Arthralgia 119701 IBIS 79 / 7739
124
 (HPO:0001387) Joint stiffness Very frequent [Orphanet] 19117856; 2512446; 3922223; 6433708 IBIS 322 / 7739
125
 (HPO:0001376) Limitation of joint mobility 813180; 119701; 3922223; 6433708 IBIS 27 / 7739
126
 (HPO:0003040) Arthropathy 19117856 IBIS 19 / 7739
127
 (HPO:0000940) Abnormal diaphysis morphology 6433708 IBIS 41 / 7739
128
 (HPO:0000943) Dysostosis multiplex Frequent [IBIS] 24675674; 19117856; 813180; 119701; 3922223; 6433708 IBIS 22 / 7739
129
 (HPO:0002208) Coarse hair 3922223 IBIS 58 / 7739
130
 (HPO:0000664) Synophrys 6433708 IBIS 112 / 7739
131
 (HPO:0001007) Hirsutism 813180 IBIS 91 / 7739
132
 (HPO:0011335) Frontal hirsutism 6433708 IBIS 4 / 7739
133
 (HPO:0002215) Sparse axillary hair 2512446 IBIS 21 / 7739
134
 (HPO:0002225) Sparse pubic hair 2512446 IBIS 76 / 7739
135
 (HPO:0002240) Hepatomegaly Frequent [IBIS] Very frequent [Orphanet] 24675674; 119701; 2512446 IBIS 467 / 7739
136
 (HPO:0001433) Hepatosplenomegaly 19117856; 811694; 813180; 119701; 3922223; 6433708 IBIS 78 / 7739
137
 (HPO:0001744) Splenomegaly Frequent [IBIS] Very frequent [Orphanet] 24675674; 119701; 6433708 IBIS 337 / 7739
138
 (HPO:0001540) Diastasis recti 3922223; 6433708 IBIS 23 / 7739
139
 (HPO:0001537) Umbilical hernia 19117856; 811694; 23917744; 119701; 2512446; 3922223; 6433708; 11131359 IBIS 206 / 7739
140
 (HPO:0004299) Hernia of the abdominal wall Very frequent [Orphanet] 19117856; 811694; 23917744; 119701; 2512446; 3922223; 6433708 IBIS 176 / 7739
141
 (HPO:0000023) Inguinal hernia 19117856; 23917744; 119701; 3922223; 6433708 IBIS 181 / 7739
142
 (HPO:0000769) Abnormality of the breast 11131359 IBIS 5 / 7739
143
 (HPO:0012569) Delayed menarche 11131359 IBIS 5 / 7739
144
 (HPO:0000034) Hydrocele testis 3922223 IBIS 18 / 7739
145
 (HPO:0001999) Abnormal facial shape 23917744; 119701; 2512446; 3922223 IBIS 169 / 7739
146
 (HPO:0000280) Coarse facial features Frequent [IBIS] Very frequent [Orphanet] 24675674; 119701; 3922223; 11131359 IBIS 189 / 7739
147
 (HPO:0012471) Thick vermilion border 811694; 119701 IBIS 115 / 7739
148
 (HPO:0000168) Abnormality of the gingiva 19117856 IBIS 51 / 7739
149
 (HPO:0000164) Abnormality of the teeth 19117856 IBIS 291 / 7739
150
 (HPO:0000682) Abnormality of dental enamel 19117856 IBIS 102 / 7739
151
 (HPO:0006482) Abnormality of dental morphology 811694 IBIS 81 / 7739
152
 (HPO:0000670) Carious teeth 19117856 IBIS 145 / 7739
153
 (HPO:0000691) Microdontia 23917744; 6433708 IBIS 104 / 7739
154
 (HPO:0000687) Widely spaced teeth 23917744; 119701; 6433708 IBIS 40 / 7739
155
 (HPO:0000463) Anteverted nares 119701 IBIS 305 / 7739
156
 (HPO:0005280) Depressed nasal bridge 119701 IBIS 381 / 7739
157
 (HPO:0001742) Nasal obstruction 3922223 IBIS 5 / 7739
158
 (HPO:0000445) Wide nose 3922223 IBIS 190 / 7739
159
 (HPO:0100765) Abnormality of the tonsils Frequent [IBIS] Very frequent [Orphanet] 24675674; 19117856; 6433708 IBIS 10 / 7739
160
 (HPO:0000405) Conductive hearing impairment 2512446 IBIS 164 / 7739
161
 (HPO:0000388) Otitis media 3922223 IBIS 28 / 7739
162
 (HPO:0000389) Chronic otitis media 119701 IBIS 64 / 7739
163
 (HPO:0000962) Hyperkeratosis 811694 IBIS 216 / 7739
164
 (HPO:0001072) Thickened skin 813180; 3922223 IBIS 87 / 7739
165
 (HPO:0100360) Contractures of the joints of the upper limbs 811694 IBIS 3 / 7739
166
 (HPO:0002828) Multiple joint contractures Frequent [IBIS] 24675674 IBIS 16 / 7739
167
 (HPO:0005876) Progressive flexion contractures 119701 IBIS 4 / 7739
168
 (HPO:0000365) Hearing impairment 119701; 6433708 IBIS 539 / 7739
169
 (HPO:0100790) Hernia Frequent [IBIS] 24675674; 813180 IBIS 9 / 7739
170
 (HPO:0012795) Abnormality of the optic disc 2512446 IBIS 187 / 7739
171
 (HPO:0002308) Arnold-Chiari malformation 23917744 IBIS 42 / 7739
172
 (HPO:0001334) Communicating hydrocephalus 19117856 IBIS 32 / 7739
173
 (HPO:0030148) Heart murmur 119701; 6433708 IBIS 29 / 7739
174
 (HPO:0030043) Hip Subluxation 19117856 IBIS 9 / 7739
175
 (HPO:0040261) Increased size of nasopharyngeal adenoids 19117856 IBIS 4 / 7739
176
 (HPO:0002196) Myelopathy Occasional [IBIS] 24675674 IBIS 6 / 7739
177
 (HPO:0002176) Spinal cord compression 19117856 IBIS 15 / 7739
178
 (HPO:0040083) Toe walking Occasional [IBIS] 24675674 IBIS 15 / 7739
179
 (MedDRA:10028017) Mouth breathing 3922223; 6433708 IBIS 1 / 7739
180
 (MedDRA:10041235) Snoring Frequent [IBIS] 24675674; 19117856 IBIS 8 / 7739
181
 (OMIM) Enlarged tonsils Frequent [IBIS] 24675674 IBIS 3 / 7739

Associated genes:

IDUA;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
IDUA rs121965020 pathogenic RCV000185562.2
IDUA rs121965027 pathogenic RCV000012694.21
IDUA rs121965029 pathogenic RCV000012697.16
IDUA rs121965031 pathogenic RCV000012699.25
IDUA rs121965032 pathogenic RCV000012700.23
IDUA rs121965033 pathogenic RCV000012702.25
IDUA rs387906504 pathogenic RCV000012695.15

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM The clinical features of Hurler-Scheie syndrome include short stature, corneal clouding, joint stiffening, umbilical hernia, dysostosis multiplex, hepatosplenomegaly, and little to no intellectual dysfunction. Onset of symptoms occurs between ages 3 and 8 years. Survival to adulthood is ...
Molecular genetics OMIM Bunge et al. (1995) identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I of differing clinical severity. ...
Population genetics OMIM Yamagishi et al. (1996) defined the IDUA mutations in 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes; Hurler syndrome, 6 cases; Hurler/Scheie syndrome, 7 cases; Scheie syndrome, 6 cases. Two common mutations ...