Polyarteritis nodosa, childhood-onset

General Information (adopted from Orphanet):

Synonyms, Signs: ADA2 deficiency
Number of Symptoms 161
OrphanetNr:
OMIM Id: 615688
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
24552285 [IBIS]
Age of onset: Infancy
Childhood
Adolescent
Adult
24552285; 29681619 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT

Comment:

Disease severity was highly varied, even within families. A total of 4 patients had mild disease limited to the skin, with no constitutional symptoms, but 13 patients had severe, often visceral, polyarteritis nodosa, which was fatal in 2 of the patients, who died at 9 months and 31 years of age, respectively (PMID:24552285). The case series revealed large phenotypic variability in 9 patients with ADA2 deficiency though they were homozygous for the same R169Q mutation in ADA2 (CECR1). In general, the authors observed a variable phenotype dominated by cutaneous and neurological symptoms. Rheumatological and inflammatory symptoms were present in the majority of patients, but they showed considerable inter-patient variability in frequency and intensity. Severity of disease course also differed strongly: several patients had disease-free intervals lasting foryears,while others (n = 3) had severe or progressive disease that required haematopoietic cell transplantation (HCT) (PMID:26867732). The phenotype and outcome observed in ADA2 deficiency (DADA2) are quite heterogeneous. Age at disease onset is usually before the second decade of life. The clinical spectrum ranges from single cutaneous lesions to severe systemic inflammatory disease with cerebral complications. Clinical and histopathological features of polyarteritis nodosa (PAN), vasculopathy-related manifestations (myalgia, hypertension and gastrointestinal symptoms), and ischaemic and haemorrhagic strokes are the most frequent DADA2 manifestations. Other clinical presentations include those resulting from immune deficiency and haematological presentations (PMID:29681619). The study identified 15 subjects with ADA2 deficiency, 5 of whom were asymptomatic (relatives of index cases; ages 5-42 years). Homozygous or compound heterozygous mutations in CECR1 were identified in all subjects. The clinical manifestations of ADA2 deficiency ranged in severity from limited cutaneous involvement to severe multisystemic vasculitis; one-third of our cases (5 of 15) were currently asymptomatic, and required close monitoring (PMID:27059682).

Symptom Information: Sort by abundance 

1
 (HPO:0002027) Abdominal pain 29681619; 27069017; 28830446; 28522451; 26233953 IBIS 184 / 7739
2
 (HPO:0011848) Abdominal colic 28024309 IBIS 8 / 7739
3
 (HPO:0002014) Diarrhea 29681619; 28522451 IBIS 225 / 7739
4
 (HPO:0002028) Chronic diarrhea 26922074 IBIS 51 / 7739
5
 (HPO:0002013) Vomiting 26867732; 27252897 IBIS 191 / 7739
6
 (HPO:0001342) Cerebral hemorrhage 24552284; 28024309; 26922074; 29681619; 27059682 IBIS 24 / 7739
7
 (HPO:0002170) Intracranial hemorrhage 26867732; 28522451 IBIS 40 / 7739
8
 (HPO:0000979) Purpura 24552285; 28522451 IBIS 27 / 7739
9
 (HPO:0000509) Conjunctivitis 28024309 IBIS 47 / 7739
10
 (HPO:0000554) Uveitis 29681619 IBIS 10 / 7739
11
 (HPO:0000648) Optic atrophy rare [HPO:skoehler] 26867732; 27059682 IBIS 238 / 7739
12
 (HPO:0100653) Optic neuritis 28522451; 26233953 IBIS 3 / 7739
13
 (HPO:0001138) Optic neuropathy 29681619 IBIS 12 / 7739
14
 (HPO:0000496) Abnormality of eye movement 26867732 IBIS 79 / 7739
15
 (HPO:0000639) Nystagmus 29681619; 28830446 IBIS 555 / 7739
16
 (HPO:0012246) Oculomotor nerve palsy 28830446 IBIS 2 / 7739
17
 (HPO:0030773) Internuclear ophthalmoplegia 29681619; 27252897 IBIS 2 / 7739
18
 (HPO:0000623) Supranuclear ophthalmoplegia 28830446 IBIS 5 / 7739
19
 (HPO:0000486) Strabismus 26867732; 26233953 IBIS 576 / 7739
20
 (HPO:0000511) Vertical supranuclear gaze palsy 28024309 IBIS 4 / 7739
21
 (HPO:0000651) Diplopia 26867732; 28830446 IBIS 37 / 7739
22
 (HPO:0000572) Visual loss 29681619 IBIS 272 / 7739
23
 (HPO:0002099) Asthma 26922074; 28493328 IBIS 62 / 7739
24
 (HPO:0002090) Pneumonia 26922074 IBIS 59 / 7739
25
 (HPO:0001611) Nasal speech 26914925 IBIS 48 / 7739
26
 (HPO:0004936) Venous thrombosis 26867732 IBIS 41 / 7739
27
 (HPO:0012490) Panniculitis 24552285 IBIS 7 / 7739
28
 (HPO:0001508) Failure to thrive 26922074 IBIS 454 / 7739
29
 (HPO:0001888) Lymphopenia 24552284; 26867732; 29681619; 29564582; 27059682; 27252897; 28493328 IBIS 43 / 7739
30
 (HPO:0011974) Myelofibrosis 26233953 IBIS 6 / 7739
31
 (HPO:0005244) Gastrointestinal infarctions 29600946 IBIS 14 / 7739
32
 (HPO:0100545) Arterial stenosis 24552285; 29600946; 27069017 IBIS 22 / 7739
33
 (HPO:0002637) Cerebral ischemia 28830446 IBIS 17 / 7739
34
 (HPO:0002140) Ischemic stroke 24552284; 29600946; 28024309; 29681619 IBIS 70 / 7739
35
 (HPO:0000822) Hypertension rare [HPO:skoehler] 24552285; 26867732; 29681619; 27069017; 28522451; 27059682; 27252897; 28493328 IBIS 224 / 7739
36
 (HPO:0001409) Portal hypertension 24552284 IBIS 39 / 7739
37
 (HPO:0001658) Myocardial infarction 28493328 IBIS 30 / 7739
38
 (HPO:0002633) Vasculitis 24552285; 29600946; 28024309; 26922074; 29681619; 27059682 IBIS 12 / 7739
39
 (HPO:0200029) Vasculitis in the skin 24552284; 24552285; 28024309; 27252897 IBIS 6 / 7739
40
 (HPO:0000824) Growth hormone deficiency 26867732; 28522451 IBIS 56 / 7739
41
 (HPO:0011227) Elevated C-reactive protein level 29600946; 29681619; 27069017; 28830446; 26914925; 27252897 IBIS 55 / 7739
42
 (HPO:0001903) Anemia rare [HPO:skoehler] 29681619; 28493328 IBIS 289 / 7739
43
 (HPO:0004840) Hypochromic microcytic anemia 26922074 IBIS 15 / 7739
44
 (HPO:0001878) Hemolytic anemia 26867732 IBIS 83 / 7739
45
 (HPO:0001935) Microcytic anemia 27252897 IBIS 32 / 7739
46
 (HPO:0005505) Refractory anemia 26867732 IBIS 2 / 7739
47
 (HPO:0010628) Facial palsy 28830446 IBIS 146 / 7739
48
 (HPO:0007209) Facial paralysis 27252897 IBIS 8 / 7739
49
 (HPO:0004313) Decreased antibody level in blood rare [HPO:skoehler] 24552284; 26867732; 29681619; 28522451; 28493328 IBIS 47 / 7739
50
 (HPO:0002720) IgA deficiency 29600946; 26922074; 29681619; 27252897; 28493328 IBIS 33 / 7739
51
 (HPO:0004315) IgG deficiency 29600946; 26922074; 27059682; 28493328 IBIS 38 / 7739
52
 (HPO:0002850) IgM deficiency 29600946; 29681619; 27059682; 27252897; 28493328; 26233953 IBIS 18 / 7739
53
 (HPO:0010702) Increased antibody level in blood 28830446 IBIS 29 / 7739
54
 (HPO:0030783) Increased serum interleukin-6 28830446 IBIS 1 / 7739
55
 (HPO:0003493) Antinuclear antibody positivity 28830446; 27252897 IBIS 15 / 7739
56
 (HPO:0002721) Immunodeficiency 29681619 IBIS 97 / 7739
57
 (HPO:0002719) Recurrent infections 24552284; 26867732; 26922074; 29681619; 28522451; 28493328 IBIS 107 / 7739
58
 (HPO:0100838) Recurrent cutaneous abscess formation 29564582 IBIS 15 / 7739
59
 (HPO:0005365) Severe B lymphocytopenia 29600946 IBIS 3 / 7739
60
 (HPO:0001913) Granulocytopenia 26867732 IBIS 5 / 7739
61
 (HPO:0004808) Acute myeloid leukemia 26867732 IBIS 14 / 7739
62
 (HPO:0001875) Neutropenia 29564582; 28493328 IBIS 83 / 7739
63
 (MedDRA:10016288) Febrile neutropenia 29564582 IBIS 1 / 7739
64
 (HPO:0100614) Myositis 29681619 IBIS 21 / 7739
65
 (HPO:0001324) Muscle weakness 29600946 IBIS 859 / 7739
66
 (HPO:0003701) Proximal muscle weakness 27252897 IBIS 105 / 7739
67
 (HPO:0003326) Myalgia 24552285; 29600946; 29681619; 27252897; 26233953 IBIS 143 / 7739
68
 (HPO:0009830) Peripheral neuropathy 24552285; 28024309; 29681619; 28522451 IBIS 206 / 7739
69
 (HPO:0001271) Polyneuropathy 27059682 IBIS 56 / 7739
70
 (HPO:0012229) CSF pleocytosis 27252897 IBIS 5 / 7739
71
 (HPO:0001291) Abnormality of the cranial nerves 28522451; 26914925; 27252897 IBIS 27 / 7739
72
 (HPO:0010827) Abnormality of the seventh cranial nerve 28522451 IBIS 1 / 7739
73
 (HPO:0006824) Cranial nerve paralysis 29681619 IBIS 81 / 7739
74
 (HPO:0002383) Encephalitis 28493328 IBIS 41 / 7739
75
 (HPO:0001287) Meningitis 29681619; 28493328 IBIS 46 / 7739
76
 (HPO:0001298) Encephalopathy 27252897 IBIS 72 / 7739
77
 (HPO:0002061) Lower limb spasticity 26914925 IBIS 56 / 7739
78
 (HPO:0011099) Spastic hemiparesis 29600946 IBIS 2 / 7739
79
 (HPO:0001285) Spastic tetraparesis 26914925 IBIS 29 / 7739
80
 (HPO:0001269) Hemiparesis 28830446; 27252897 IBIS 51 / 7739
81
 (HPO:0001251) Ataxia 26867732; 28024309; 28830446; 26914925; 27252897 IBIS 413 / 7739
82
 (HPO:0002321) Vertigo 26867732; 29681619; 28830446; 27252897 IBIS 58 / 7739
83
 (HPO:0012433) Abnormal social behavior 26867732 IBIS 7 / 7739
84
 (HPO:0002381) Aphasia 27252897 IBIS 27 / 7739
85
 (HPO:0001260) Dysarthria 26914925 IBIS 329 / 7739
86
 (HPO:0012378) Fatigue 28830446 IBIS 50 / 7739
87
 (HPO:0001288) Gait disturbance 27252897 IBIS 318 / 7739
88
 (HPO:0002015) Dysphagia 26914925 IBIS 301 / 7739
89
 (HPO:0002315) Headache 26867732; 29681619; 28830446; 27252897 IBIS 175 / 7739
90
 (HPO:0001250) Seizures 26867732; 29681619 IBIS 1245 / 7739
91
 (HPO:0002829) Arthralgia 24552285; 26867732; 28024309; 26922074; 29681619; 27069017; 28830446; 28522451; 28493328; 26233953 IBIS 79 / 7739
92
 (HPO:0001369) Arthritis 29681619; 28830446; 28522451 IBIS 44 / 7739
93
 (HPO:0100769) Synovitis 28830446 IBIS 86 / 7739
94
 (HPO:0001596) Alopecia 28493328 IBIS 162 / 7739
95
 (HPO:0001945) Fever 24552284; 24552285; 28024309; 26922074; 29681619; 27069017; 28830446; 28522451; 27252897; 28493328; 26233953 IBIS 218 / 7739
96
 (HPO:0011024) Abnormality of the gastrointestinal tract 24552285 IBIS 5 / 7739
97
 (HPO:0002242) Abnormality of the intestine 28493328 IBIS 42 / 7739
98
 (HPO:0002583) Colitis 28493328 IBIS 9 / 7739
99
 (HPO:0002576) Intussusception 28522451 IBIS 10 / 7739
100
 (HPO:0004386) Gastrointestinal inflammation 29564582 IBIS 5 / 7739
101
 (HPO:0012115) Hepatitis 28493328 IBIS 24 / 7739
102
 (HPO:0002240) Hepatomegaly 24552284; 26867732; 29681619; 28522451; 28493328; 26233953 IBIS 467 / 7739
103
 (HPO:0001733) Pancreatitis 26233953 IBIS 46 / 7739
104
 (HPO:0001744) Splenomegaly 24552284; 26867732; 26922074; 29681619; 28522451; 28493328; 26233953 IBIS 337 / 7739
105
 (HPO:0001638) Cardiomyopathy 26867732 IBIS 192 / 7739
106
 (HPO:0001701) Pericarditis 29681619 IBIS 13 / 7739
107
 (HPO:0001680) Coarctation of aorta 27059682 IBIS 57 / 7739
108
 (HPO:0000155) Oral ulcer 26922074; 29681619; 29564582; 28830446; 28522451 IBIS 9 / 7739
109
 (HPO:0011107) Recurrent aphthous stomatitis 24552285 IBIS 13 / 7739
110
 (HPO:0000407) Sensorineural hearing impairment 28522451 IBIS 524 / 7739
111
 (HPO:0008940) Generalized lymphadenopathy 28522451 IBIS 14 / 7739
112
 (HPO:0002716) Lymphadenopathy 28493328 IBIS 129 / 7739
113
 (HPO:0000951) Abnormality of the skin 28830446 IBIS 147 / 7739
114
 (HPO:0000965) Cutis marmorata 24552284; 24552285; 28024309; 29681619; 27069017; 28830446; 28522451; 27059682; 26914925; 28493328; 26233953 IBIS 46 / 7739
115
 (HPO:0011123) Inflammatory abnormality of the skin 26867732 IBIS 10 / 7739
116
 (HPO:0000964) Eczema 28493328 IBIS 81 / 7739
117
 (HPO:0012219) Erythema nodosum 24552285; 26922074; 29681619; 27069017; 28493328; 26233953 IBIS 3 / 7739
118
 (HPO:0003765) Psoriasis 28522451 IBIS 17 / 7739
119
 (HPO:0200036) Skin nodule 24552285 IBIS 4 / 7739
120
 (HPO:0001482) Subcutaneous nodule 28522451 IBIS 17 / 7739
121
 (HPO:0200043) Verrucae 28493328 IBIS 11 / 7739
122
 (HPO:0000989) Pruritus 29681619 IBIS 111 / 7739
123
 (HPO:0001025) Urticaria 29681619; 28522451 IBIS 73 / 7739
124
 (HPO:0200042) Skin ulcer 24552285; 26867732; 28493328; 26233953 IBIS 138 / 7739
125
 (HPO:0000097) Focal segmental glomerulosclerosis 26233953 IBIS 37 / 7739
126
 (HPO:0001970) Tubulointerstitial nephritis 26922074 IBIS 27 / 7739
127
 (HPO:0000126) Hydronephrosis 26922074 IBIS 119 / 7739
128
 (HPO:0001917) Renal amyloidosis 26233953 IBIS 8 / 7739
129
 (HPO:0000790) Hematuria 24552285; 29681619 IBIS 106 / 7739
130
 (HPO:0000123) Nephritis 28493328 IBIS 18 / 7739
131
 (MedDRA:10038470) Renal infarct 27069017 IBIS 1 / 7739
132
 (HPO:0000083) Renal insufficiency 28493328 IBIS 232 / 7739
133
 (HPO:0000093) Proteinuria 24552285 IBIS 169 / 7739
134
 (HPO:0002597) Abnormality of the vasculature 26914925 IBIS 5 / 7739
135
 (HPO:0001297) Stroke 24552284; 28522451; 27059682; 27252897; 28493328; 26233953 IBIS 44 / 7739
136
 (HPO:0002617) Aneurysm 24552285; 29681619; 27059682 IBIS 34 / 7739
137
 (HPO:0001873) Thrombocytopenia 26867732; 28493328 IBIS 224 / 7739
138
 (HPO:0011034) Amyloidosis 26233953 IBIS 12 / 7739
139
 (HPO:0003565) Elevated erythrocyte sedimentation rate 29600946; 28024309; 27069017; 28830446; 26914925; 27252897 IBIS 31 / 7739
140
 (HPO:0000365) Hearing impairment 26867732 IBIS 539 / 7739
141
 (HPO:3000042) Abnormality of jugular vein 26867732 IBIS 1 / 7739
142
 (HPO:0410008) Abnormality of the peripheral nervous system 24552285 IBIS 1 / 7739
143
 (HPO:0000238) Hydrocephalus 26867732 IBIS 278 / 7739
144
 (HPO:0030348) Increased circulating androgen level 29681619 IBIS 8 / 7739
145
 (HPO:0040186) Maculopapular exanthema 28024309; 29681619 IBIS 2 / 7739
146
 (HPO:0012819) Myocarditis 28522451 IBIS 4 / 7739
147
 (HPO:0030880) Raynaud phenomenon 24552285; 28024309; 29681619; 28830446; 26914925 IBIS 2 / 7739
148
 (HPO:0007236) Recurrent subcortical infarcts 24552284 IBIS 2 / 7739
149
 (MedDRA:10006513) Bruising, ecchymosis and purpura 28522451 IBIS 3 / 7739
150
 (MedDRA:10008118) Cerebral infarction 24552285 IBIS 10 / 7739
151
 (MedDRA:10016936) Folliculitis 29681619 IBIS 5 / 7739
152
 (MedDRA:10065597) Hyperandrogenism 29681619 IBIS 4 / 7739
153
 (MedDRA:10068237) Hypertransaminasaemia 26233953 IBIS 1 / 7739
154
 (MedDRA:10066315) Interleukin-2 receptor increased 28830446 IBIS 1 / 7739
155
 (MedDRA:10024377) Leukocytoclastic vasculitis 24552285; 28522451 IBIS 1 / 7739
156
 (MedDRA:10050206) Macrophage activation 26233953 IBIS 1 / 7739
157
 (MedDRA:10034576) Peripheral ischaemia 27059682 IBIS 1 / 7739
158
 (MedDRA:10059361) Pleuropericarditis 29681619 IBIS 1 / 7739
159
 (MedDRA:10055672) Pneumonia necrotising 26233953 IBIS 1 / 7739
160
 (MedDRA:10036024) Polyarteritis nodosa 24552284; 24552285; 29681619; 28522451; 27059682; 28493328 IBIS 1 / 7739
161
 (MedDRA:10043345) Testicular pain 24552285 IBIS 1 / 7739

Associated genes:

ADA2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information: