Fucosidosis

General Information (adopted from Orphanet):

Synonyms, Signs: alpha-l-fucosidase deficiency
Number of Symptoms 81
OrphanetNr: 349
OMIM Id: 230000
ICD-10: E77.1
UMLs:
MeSH: D005645
MedDRA:
Snomed: 64716005

Prevalence, inheritance and age of onset:

Prevalence: < 100 cases - PMID: 26622931 [IBIS]
Inheritance: Autosomal recessive
- PMID: 10571005 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Developmental anomaly of metabolic origin
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Lysosomal disease with hypertrophic cardiomyopathy
 -Rare cardiac disease
 -Rare genetic disease
Lysosomal storage disease with skeletal involvement
 -Rare bone disease
 -Rare genetic disease
Oligosaccharidosis
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Comment:

Two clinical subtypes, type 1 and 2 are generally differentiated . Type 1 is described as the severe infantile form with a general deterioration of the neurological functions at the age of 1 or 2 years. Type 2 is a milder form; symptoms appear progressively and the patients survive into the second or third decade of life (PMID:10571005).

Symptom Information: Sort by abundance 

1
 (HPO:0000503) Tortuosity of conjunctival vessels 2721986 IBIS 3 / 7739
2
 (HPO:0000316) Hypertelorism 15214749 IBIS 644 / 7739
3
 (HPO:0000481) Abnormality of the cornea Frequent [Orphanet] 2721986 IBIS 124 / 7739
4
 (HPO:0002205) Recurrent respiratory infections Frequent [Orphanet] 24636010 IBIS 254 / 7739
5
 (HPO:0004322) Short stature 25818965 IBIS 1232 / 7739
6
 (HPO:0004325) Decreased body weight Very frequent [Orphanet] 26713028 IBIS 492 / 7739
7
 (HPO:0001508) Failure to thrive 24636010 IBIS 454 / 7739
8
 (HPO:0011020) Abnormality of mucopolysaccharide metabolism Very frequent [Orphanet] 26622931 IBIS 17 / 7739
9
 (HPO:0012067) Glycopeptiduria 10571005 IBIS 1 / 7739
10
 (HPO:0010471) Oligosacchariduria 10571005 IBIS 4 / 7739
11
 (HPO:0001640) Cardiomegaly Occasional [Orphanet] 11290499 IBIS 81 / 7739
12
 (HPO:0002719) Recurrent infections Frequent [IBIS] 78% (n=77) 2012122 IBIS 107 / 7739
13
 (HPO:0012236) Elevated sweat chloride 814528 IBIS 5 / 7739
14
 (HPO:0001922) Vacuolated lymphocytes 2721986 IBIS 13 / 7739
15
 (HPO:0003202) Skeletal muscle atrophy Frequent [Orphanet] 9762612 IBIS 281 / 7739
16
 (HPO:0000158) Macroglossia 24636010 IBIS 119 / 7739
17
 (HPO:0001252) Muscular hypotonia Frequent [Orphanet] 26622931 IBIS 990 / 7739
18
 (HPO:0001324) Muscle weakness 24636010 IBIS 859 / 7739
19
 (HPO:0011442) Abnormality of central motor function Very frequent [Orphanet] 814528 IBIS 76 / 7739
20
 (HPO:0001310) Dysmetria 11290499 IBIS 76 / 7739
21
 (HPO:0007256) Abnormal pyramidal signs Occasional [Orphanet] 24636010 IBIS 116 / 7739
22
 (HPO:0001347) Hyperreflexia 26622931 IBIS 363 / 7739
23
 (HPO:0001276) Hypertonia Frequent [Orphanet] 24636010 IBIS 317 / 7739
24
 (HPO:0002064) Spastic gait 26622931 IBIS 46 / 7739
25
 (HPO:0002510) Spastic tetraplegia 24636010 IBIS 54 / 7739
26
 (HPO:0001332) Dystonia 24636010 IBIS 197 / 7739
27
 (HPO:0007272) Progressive psychomotor deterioration Very frequent [IBIS] 2012122 IBIS 6 / 7739
28
 (HPO:0001249) Intellectual disability 10571005 IBIS 1089 / 7739
29
 (HPO:0000750) Delayed speech and language development 26622931 IBIS 197 / 7739
30
 (HPO:0001288) Gait disturbance 814528 IBIS 318 / 7739
31
 (HPO:0001250) Seizures Frequent [Orphanet] Frequent [IBIS] 38% (n=77) 2012122 IBIS 1245 / 7739
32
 (HPO:0002673) Coxa valga 814528 IBIS 57 / 7739
33
 (HPO:0003170) Abnormality of the acetabulum 25250075 IBIS 3 / 7739
34
 (HPO:0002644) Abnormality of pelvic girdle bone morphology 814528 IBIS 31 / 7739
35
 (HPO:0000256) Macrocephaly 11290499 IBIS 298 / 7739
36
 (HPO:0003312) Abnormal form of the vertebral bodies Very frequent [Orphanet] 26622931 IBIS 172 / 7739
37
 (HPO:0008430) Anterior beaking of lumbar vertebrae 26622931 IBIS 5 / 7739
38
 (HPO:0004630) Anterior beaking of thoracic vertebrae 26622931 IBIS 1 / 7739
39
 (HPO:0003311) Hypoplasia of the odontoid process 814528 IBIS 34 / 7739
40
 (HPO:0002808) Kyphosis Very frequent [Orphanet] 26622931 IBIS 289 / 7739
41
 (HPO:0002751) Kyphoscoliosis 11290499 IBIS 131 / 7739
42
 (HPO:0002650) Scoliosis 26622931 IBIS 705 / 7739
43
 (HPO:0000939) Osteoporosis 26622931 IBIS 129 / 7739
44
 (HPO:0005622) Broad long bones 26622931 IBIS 8 / 7739
45
 (HPO:0000943) Dysostosis multiplex Frequent [IBIS] 58% (n=77) 2012122 IBIS 22 / 7739
46
 (HPO:0002652) Skeletal dysplasia Very frequent [Orphanet] 25818965 IBIS 113 / 7739
47
 (HPO:0002750) Delayed skeletal maturation 26622931 IBIS 250 / 7739
48
 (HPO:0002553) Highly arched eyebrow 24636010 IBIS 92 / 7739
49
 (HPO:0000970) Anhidrosis 11290499 IBIS 24 / 7739
50
 (HPO:0000975) Hyperhidrosis 814528 IBIS 64 / 7739
51
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 11290499 IBIS 467 / 7739
52
 (HPO:0006568) Increased hepatic glycogen content Frequent [Orphanet] 10571005 IBIS 34 / 7739
53
 (HPO:0001744) Splenomegaly Frequent [Orphanet] 11290499 IBIS 337 / 7739
54
 (HPO:0003271) Visceromegaly Frequent [IBIS] 44% (n=77) 2012122 IBIS 8 / 7739
55
 (HPO:0004298) Abnormality of the abdominal wall 15214749 IBIS 20 / 7739
56
 (HPO:0001626) Abnormality of the cardiovascular system Frequent [Orphanet] 814528 IBIS 73 / 7739
57
 (HPO:0001999) Abnormal facial shape Very frequent [Orphanet] 24636010 IBIS 169 / 7739
58
 (HPO:0000280) Coarse facial features Very frequent [Orphanet] Frequent [IBIS] 79% (n=77) 2012122 IBIS 189 / 7739
59
 (HPO:0000212) Gingival overgrowth 24636010 IBIS 43 / 7739
60
 (HPO:0000164) Abnormality of the teeth Occasional [Orphanet] 814528 IBIS 291 / 7739
61
 (HPO:0000405) Conductive hearing impairment 26622931 IBIS 164 / 7739
62
 (HPO:0000389) Chronic otitis media 26622931 IBIS 64 / 7739
63
 (HPO:0000958) Dry skin 24636010 IBIS 152 / 7739
64
 (HPO:0000962) Hyperkeratosis Very frequent [Orphanet] 814528 IBIS 216 / 7739
65
 (HPO:0011276) Vascular skin abnormality Very frequent [Orphanet] 2012122 IBIS 24 / 7739
66
 (HPO:0001014) Angiokeratoma Frequent [IBIS] 24636010 IBIS 5 / 7739
67
 (HPO:0001071) Angiokeratoma corporis diffusum Frequent [IBIS] 52% (n=77) 2012122 IBIS 7 / 7739
68
 (HPO:0001009) Telangiectasia 11290499 IBIS 46 / 7739
69
 (HPO:0000821) Hypothyroidism Very frequent [Orphanet] 15214749 IBIS 141 / 7739
70
 (HPO:0001371) Flexion contracture 24636010 IBIS 220 / 7739
71
 (HPO:0001510) Growth delay Frequent [IBIS] 78% (n=77) 2012122 IBIS 295 / 7739
72
 (HPO:0000365) Hearing impairment Very frequent [Orphanet] 11290499 IBIS 539 / 7739
73
 (HPO:0100790) Hernia 11290499 IBIS 9 / 7739
74
 (HPO:0002500) Abnormality of the cerebral white matter 11290499 IBIS 73 / 7739
75
 (HPO:0002453) Abnormality of the globus pallidus 26713028 IBIS 4 / 7739
76
 (HPO:0001272) Cerebellar atrophy 11290499 IBIS 197 / 7739
77
 (HPO:0002059) Cerebral atrophy 11290499 IBIS 171 / 7739
78
 (HPO:0006808) Cerebral hypomyelination 24636010 IBIS 16 / 7739
79
 (HPO:0002454) Eye of the tiger anomaly of globus pallidus 24636010 IBIS 3 / 7739
80
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 10571005 IBIS 949 / 7739
81
 (OMIM) Alpha-L-fucosidase deficiency 10571005 IBIS 1 / 7739

Associated genes:

FUCA1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
FUCA1 rs118204450 pathogenic RCV000000716.2
FUCA1 rs587779398 pathogenic RCV000087085.1
FUCA1 rs587779399 pathogenic RCV000087086.1
FUCA1 rs794727774 pathogenic RCV000179259.1
FUCA1 rs80358195 pathogenic RCV000000718.2
FUCA1 rs80358196 pathogenic RCV000000720.2
FUCA1 rs80358197 pathogenic RCV000000721.2
FUCA1 rs80358198 pathogenic RCV000000722.2
FUCA1 rs80358199 pathogenic RCV000000727.2

Additional Information:

Description: (OMIM) Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex.

Fucosidosis has ...
Clinical Description OMIM Van Hoof and Hers (1968) found deficiency of alpha-fucosidase activity in the liver of patients with a Hurler-like disorder described by Durand et al. (1967, 1968). Fucose accumulated in all tissues (Durand et al., 1969). Durand et al. ...
Molecular genetics OMIM Darby et al. (1988) found 2 RFLPs in the FUCA gene in Caucasians; the polymorphism information content (PIC) of the combined DNA markers was 0.38. No recombinants were observed between fucosidosis phenotype and these RFLP markers, suggesting that ...
Population genetics OMIM A majority of earlier-reported cases of fucosidosis were Italian; most of these patients originated from 2 neighboring villages, Grotteria and Mammola, in the southern Italian province of Reggio Calabria (Sangiorgi et al., 1982).

Willems et al. ...