Cystinosis

General Information (adopted from Orphanet):

Synonyms, Signs: Protein defect of cystin transport
Number of Symptoms 104
OrphanetNr: 213
OMIM Id: 219750
219800
219900
ICD-10: E72.0
UMLs: C0010690
MeSH: D003554
MedDRA: 10011777
Snomed: 190681003

Prevalence, inheritance and age of onset:

Prevalence: 0.5 of 100 000
Inheritance: Autosomal recessive
22903658 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of lysosomal amino acid transport
 -Rare genetic disease

Comment:

Nephropathic or classic infantile cystinosis (OMIM:219800), the most severe form, is the major identifiable cause of renal Fanconi syndrome in children. The intermediate (juvenile) form of cystinosis (OMIM:219900) has all the manifestations of the nephropathic form, but its onset is generally around the time of adolescence (PMID:22903658).

Symptom Information: Sort by abundance 

1
(HPO:0000078) Abnormality of the genital system Very frequent [Orphanet] 25165189 IBIS 33 / 7739
2
(HPO:0000026) Male hypogonadism 25165189 IBIS 20 / 7739
3
(HPO:0000093) Proteinuria Very frequent [Orphanet] 22903658 IBIS 169 / 7739
4
(HPO:0000103) Polyuria Very frequent [Orphanet] 22903658 IBIS 60 / 7739
5
(HPO:0012213) Decreased glomerular filtration rate 25394439 IBIS 21 / 7739
6
(HPO:0000135) Hypogonadism Very frequent [Orphanet] 25165189 IBIS 89 / 7739
7
(HPO:0000091) Abnormality of the renal tubule Very frequent [Orphanet] 22903658 IBIS 15 / 7739
8
(HPO:0000124) Renal tubular dysfunction Very frequent [Orphanet] 25165189 IBIS 46 / 7739
9
(HPO:0003076) Glycosuria 22903658 IBIS 32 / 7739
10
(HPO:0000787) Nephrolithiasis 19156444 IBIS 78 / 7739
11
(HPO:0002907) Microscopic hematuria 7742221 IBIS 27 / 7739
12
(HPO:0003251) Male infertility 25165189 IBIS 14 / 7739
13
(HPO:0001994) Renal Fanconi syndrome 25165189 IBIS 12 / 7739
14
(HPO:0003646) Bicarbonaturia 24255892 IBIS 3 / 7739
15
(HPO:0000121) Nephrocalcinosis 22903658 IBIS 57 / 7739
16
(HPO:0011038) Abnormality of renal resorption Very frequent [Orphanet] 25165189 IBIS 6 / 7739
17
(HPO:0000112) Nephropathy Very frequent [Orphanet] 22903658 IBIS 92 / 7739
18
(HPO:0003109) Hyperphosphaturia 24255892 IBIS 18 / 7739
19
(HPO:0000083) Renal insufficiency Frequent [Orphanet] 22903658 IBIS 232 / 7739
20
(HPO:0100820) Glomerulopathy 25394439 IBIS 46 / 7739
21
(HPO:0003355) Aminoaciduria Very frequent [Orphanet] 22903658 IBIS 65 / 7739
22
(HPO:0002007) Frontal bossing 21750641 IBIS 366 / 7739
23
(HPO:0010628) Facial palsy Occasional [Orphanet] occasional [HPO] 11516611 IBIS 146 / 7739
24
(HPO:0200020) Corneal erosion 17212992 IBIS 12 / 7739
25
(HPO:0000613) Photophobia Very frequent [Orphanet] 22903658 IBIS 158 / 7739
26
(HPO:0000488) Retinopathy Frequent [Orphanet] 17212992 IBIS 75 / 7739
27
(HPO:0000505) Visual impairment Occasional [Orphanet] 17212992 IBIS 297 / 7739
28
(HPO:0000531) Corneal crystals 22903658 IBIS 9 / 7739
29
(HPO:0007957) Corneal opacity Very frequent [Orphanet] hallmark [HPO] 17212992 IBIS 84 / 7739
30
(HPO:0007759) Opacification of the corneal stroma Very frequent [Orphanet] 17212992 IBIS 77 / 7739
31
(HPO:0011496) Corneal neovascularization Very frequent [Orphanet] 25165189 IBIS 7 / 7739
32
(HPO:0002275) Poor motor coordination Frequent [IBIS] 60% (n=52) 20652328; 24077756 IBIS 6 / 7739
33
(HPO:0006824) Cranial nerve paralysis Occasional [Orphanet] 7957435 IBIS 81 / 7739
34
(HPO:0001270) Motor delay Occasional [Orphanet] 25165189 IBIS 322 / 7739
35
(HPO:0001269) Hemiparesis 7957435 IBIS 51 / 7739
36
(HPO:0001263) Global developmental delay Occasional [Orphanet] 25394439 IBIS 853 / 7739
37
(HPO:0001347) Hyperreflexia 7957435 IBIS 363 / 7739
38
(HPO:0003473) Fatigable weakness Very frequent [Orphanet] 25715639 IBIS 39 / 7739
39
(HPO:0002381) Aphasia Occasional [Orphanet] 25165189 IBIS 27 / 7739
40
(HPO:0002354) Memory impairment 25165189 IBIS 63 / 7739
41
(HPO:0002357) Dysphasia Occasional [Orphanet] 25165189 IBIS 33 / 7739
42
(HPO:0002167) Neurological speech impairment Occasional [Orphanet] 25165189 IBIS 308 / 7739
43
(HPO:0000726) Dementia 25165189 IBIS 131 / 7739
44
(HPO:0002516) Increased intracranial pressure 22903658 IBIS 47 / 7739
45
(HPO:0001959) Polydipsia 22903658 IBIS 43 / 7739
46
(HPO:0100543) Cognitive impairment Occasional [Orphanet] 25165189 IBIS 230 / 7739
47
(HPO:0001288) Gait disturbance Occasional [Orphanet] 19294426 IBIS 318 / 7739
48
(HPO:0001328) Specific learning disability Occasional [Orphanet] 25394439 IBIS 114 / 7739
49
(HPO:0010794) Impaired visuospatial constructive cognition 25394439 IBIS 3 / 7739
50
(HPO:0000708) Behavioral abnormality 25394439 IBIS 212 / 7739
51
(HPO:0001249) Intellectual disability Occasional [Orphanet] 25394439 IBIS 1089 / 7739
52
(HPO:0002015) Dysphagia Frequent [IBIS] 15879904 IBIS 301 / 7739
53
(HPO:0000733) Stereotypy Very frequent [Orphanet] 25394439 IBIS 58 / 7739
54
(HPO:0000823) Delayed puberty Very frequent [Orphanet] 22903658 IBIS 65 / 7739
55
(HPO:0100651) Type I diabetes mellitus Very frequent [Orphanet] 25165189 IBIS 44 / 7739
56
(HPO:0000873) Diabetes insipidus Very frequent [Orphanet] 20733335 IBIS 34 / 7739
57
(HPO:0000821) Hypothyroidism Very frequent [Orphanet] 22903658 IBIS 141 / 7739
58
(HPO:0000938) Osteopenia Frequent [Orphanet] 24077756 IBIS 138 / 7739
59
(HPO:0002749) Osteomalacia Frequent [Orphanet] 24077756 IBIS 24 / 7739
60
(HPO:0000939) Osteoporosis Frequent [Orphanet] 1233351 IBIS 129 / 7739
61
(HPO:0002857) Genu valgum 24077756 IBIS 144 / 7739
62
(HPO:0011842) Abnormality of skeletal morphology 24077756 IBIS 1 / 7739
63
(HPO:0011849) Abnormal bone ossification 24077756 IBIS 35 / 7739
64
(HPO:0002748) Rickets Frequent [Orphanet] 22903658; 24077756 IBIS 41 / 7739
65
(HPO:0001216) Delayed ossification of carpal bones 24077756 IBIS 30 / 7739
66
(HPO:0002024) Malabsorption Occasional [Orphanet] 22903658 IBIS 142 / 7739
67
(HPO:0002019) Constipation Occasional [IBIS] 17.4% (n=23) 19841525 IBIS 194 / 7739
68
(HPO:0001744) Splenomegaly Occasional [IBIS] 21.7% (n=23) 19841525 IBIS 337 / 7739
69
(HPO:0002028) Chronic diarrhea Occasional [Orphanet] 11516611 IBIS 51 / 7739
70
(HPO:0002027) Abdominal pain Occasional [IBIS] 13.0% (n=23) 19841525 IBIS 184 / 7739
71
(HPO:0011968) Feeding difficulties Very frequent [Orphanet] 11516611 IBIS 240 / 7739
72
(HPO:0001409) Portal hypertension Occasional [Orphanet] 21360162 IBIS 39 / 7739
73
(HPO:0002013) Vomiting Very frequent [Orphanet] 11516611 IBIS 191 / 7739
74
(HPO:0002039) Anorexia Occasional [IBIS] 17.4% (n=23) 19841525; 24077756 IBIS 62 / 7739
75
(HPO:0012093) Abnormality of endocrine pancreas physiology 3307383 IBIS 4 / 7739
76
(HPO:0002240) Hepatomegaly Frequent [IBIS] 34.8% (n=23) 19841525 IBIS 467 / 7739
77
(HPO:0002018) Nausea Very frequent [Orphanet] hallmark [HPO] 19841525 IBIS 44 / 7739
78
(HPO:0001738) Exocrine pancreatic insufficiency 3335962 IBIS 23 / 7739
79
(HPO:0001510) Growth delay Very frequent [Orphanet] 22903658 IBIS 295 / 7739
80
(HPO:0004325) Decreased body weight 25394439 IBIS 492 / 7739
81
(HPO:0003510) Severe short stature Very frequent [Orphanet] 25394439 IBIS 90 / 7739
82
(HPO:0004322) Short stature Very frequent [Orphanet] 25394439 IBIS 1232 / 7739
83
(HPO:0001508) Failure to thrive Very frequent [Orphanet] 22903658 IBIS 454 / 7739
84
(HPO:0005599) Hypopigmentation of hair Frequent [IBIS] 85 % (n=21) 22649030 IBIS 38 / 7739
85
(HPO:0001010) Hypopigmentation of the skin Frequent [IBIS] 44 % (n=27) 22649030 IBIS 46 / 7739
86
(HPO:0002148) Hypophosphatemia Very frequent [Orphanet] 22903658 IBIS 43 / 7739
87
(HPO:0004337) Abnormality of amino acid metabolism Very frequent [Orphanet] 22903658 IBIS 45 / 7739
88
(HPO:0001944) Dehydration Very frequent [Orphanet] 22903658 IBIS 59 / 7739
89
(HPO:0002900) Hypokalemia Very frequent [Orphanet] 24255892 IBIS 45 / 7739
90
(HPO:0004370) Abnormality of temperature regulation Occasional [Orphanet] 6726525 IBIS 58 / 7739
91
(HPO:0002902) Hyponatremia 24255892 IBIS 37 / 7739
92
(HPO:0003234) Decreased plasma carnitine 22903658 IBIS 9 / 7739
93
(HPO:0001945) Fever Occasional [Orphanet] 21750641 IBIS 218 / 7739
94
(HPO:0003358) Elevated intracellular cystine 22903658 IBIS 4 / 7739
95
(HPO:0001608) Abnormality of the voice 11516611 IBIS 126 / 7739
96
(HPO:0002093) Respiratory insufficiency 25165189 IBIS 410 / 7739
97
(HPO:0001324) Muscle weakness Very frequent [Orphanet] 25165189 IBIS 859 / 7739
98
(HPO:0010547) Muscle flaccidity Very frequent [Orphanet] 24255892 IBIS 466 / 7739
99
(HPO:0003202) Skeletal muscle atrophy 17709758 IBIS 281 / 7739
100
(HPO:0003198) Myopathy Very frequent [Orphanet] 25165189 IBIS 151 / 7739
101
(HPO:0001252) Muscular hypotonia Very frequent [Orphanet] hallmark [HPO] 11516611 IBIS 990 / 7739
102
(HPO:0002059) Cerebral atrophy 25394439 IBIS 171 / 7739
103
(HPO:0002500) Abnormality of the cerebral white matter 25165189 IBIS 73 / 7739
104
(MedDRA:10043458) Thirst Very frequent [Orphanet] 22903658 IBIS 2 / 7739

Associated genes:

CTNS;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis GeneReviews Nephropathic cystinosis (classic/infantile/early onset). The diagnosis of classic nephropathic cystinosis depends on the findings of renal tubular Fanconi syndrome in the untreated child in the first year of life, growth retardation after age six months, and progressive deterioration of renal glomerular function to end-stage renal disease (ESRD) over the first ten years of life [Gahl et al 2001, Gahl et al 2002]. ...
Clinical Description GeneReviews The three types of cystinosis, i.e., nephropathic (classic renal and systemic disease), intermediate (a late-onset variant of nephropathic cystinosis), and non-nephropathic (clinically affecting only the cornea) are allelic disorders caused by CTNS mutations [Thoene et al 1999, Anikster et al 2000]. ...
Genotype-Phenotype Correlations GeneReviews Some genotype-phenotype correlations can be made:...
Differential Diagnosis GeneReviews Untreated nephropathic cystinosis is the most common identifiable cause of the renal tubular Fanconi syndrome in childhood. Other causes:...
Management GeneReviews At the time of diagnosis, the following evaluations are recommended in all individuals with cystinosis regardless of age:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....