Table 2 Clinical manifestation of DADA2 patients so far described
From: Monogenic polyarteritis: the lesson of ADA2 deficiency
Report | CECR1 Mutation | Ethnicity | Age at onset | Fever | Skin | CNS/PNS | Gastro-intestinal | Immune/Hematologic system | ANA | ANCA | Hypertension | Other | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Navon et al. | 1 | G47R/G47R | Georgian | 2 m | Yes | Ulcerations at extremities | No | Intestinal necrosis | No | neg | neg | Yes | Coronary aneurysms |
2 | G47R/G47R | Georgian | 5 y | No | Livedo reticularis, nodules, purpuric rash | No | Intestinal vasculitis | No | neg | neg | No | No | |
3 | G47R/G47R | Georgian | 7 m | Yes | Livedo reticularis, papulo-nodular rash, Raynaud’s phenomenon | Ischemic stroke, peripheral paresis of cranial nerves | No | No | neg | neg | Yes | Arthritis | |
4 | G47R/G47R | Georgian | 3,5 y | Yes | Livedo reticularis, nodules, purpuric rash, erythema nodosum | Cranial nerve paralysis | No | No | pos | ND | No | No | |
5 | G47R/G47R | Georgian | 2,5 y | No | Maculopapular rash, nodules | Neurosensorial hearing loss | No | No | neg | neg | No | Arthritis | |
6 | G47R/G47R | Georgian | 2 m (died at 9 m) | Yes | Digital necrosis | Ventricular haemorrhage | Aneurism of celiac artery | No | neg | neg | No | No | |
7 | G47R/G47R | Georgian | 2 m | Yes | Livedo reticularis, Raynaud’s phenomenon | No | Abdominal pain | No | neg | ND | No | No | |
8 | G47R/G47R | Georgian | 6,5 y | Yes | Livedo reticularis, nodules, Raynaud’s phenomenon | No | Abdominal pain | No | neg | neg | No | No | |
9 | G47R/G47R | Georgian | 9 y | No | Livedo reticularis | No | No | No | neg | neg | No | No | |
10 | G47R/G47R | Georgian | 10 y | No | Livedo reticularis, nodules, Raynaud’s phenomenon, leg ulcers | No | No | No | neg | neg | No | No | |
11 | G47R/G47R | Georgian | 59 y | No | Leg ulcers | No | No | No | neg | ND | No | No | |
12 | G47R/G47R | Georgian | childhood (died at 30 y) | No | Livedo reticularis, nodules, Raynaud’s phenomenon, leg ulcers with amputation | No | No | No | ND | ND | No | No | |
13 | G47R/G47R | Georgian | 1 y | No | Livedo reticularis, nodules, Raynaud’s phenomenon | Sensitive polyneuropathy | No | No | neg | neg | No | No | |
14 | G47R/G47R | Georgian | 4 y | Yes | Livedo reticularis, purpuric rash, skin nodules. | No | No | No | pos | ND | No | No | |
15 | G47R/G47R | Georgian | 1 y | Yes | Livedo reticularis | No | Abdominal pain | No | neg | neg | Yes | Mesenteric and renal infarcts | |
16 | G47R/G47R | Georgian | 18 y | No | No | No | No | No | neg | neg | No | No | |
17 | G47R/G47R | Georgian | 28 y | Yes | Raynaud’s phenomenon, purpuric rash, leg ulcers with digital amputation | Polyneuropathy | No | No | neg | neg | Yes | Panniculitis | |
18 | G47R/G47R | Georgian | 2 y | No | Skin nodules | Polyneuropathy | No | No | neg | neg | No | No | |
19 | G47R/G47R | Georgian | 16 y | No | Raynaud’s phenomenon, ulceration of extremities | No | No | No | pos | neg | Yes | No | |
20 | R169Q/P251L | European Caucasian | 1 y | Yes | Livedo reticularis | Ischemic stroke, cranial nerves (II,VI,VII) paralysis | No | No | neg | ND | Yes | No | |
21 | R169Q/P251L | European Caucasian | 12 y | No | No | Ischemic stroke, VII cranial nerve paralysis | No | No | pos | neg | No | No | |
22 | R169Q/P251L | European Caucasian | 1 y | No | Livedo reticularis, skin rash at extremities | Ischemic stroke VI cranial nerve paralysis, neurosensorial hearing loss | No | No | neg | neg | No | No | |
23 | R169Q/P251L | European Caucasian | 3 m | No | Livedo reticularis, vasculitic exanthema of lower extremities | VII cranial nerve paralysis | No | No | ND | ND | No | Epididymitis | |
24 | G47V/W264S | Turkish | 10 y | Yes | Livedo reticularis | No | No | No | neg | ND | Yes | Myalgia, abdominal and renal aneurysm | |
Zhou et al. | 1 | A109D/Y453C | European Caucasian | 2 y | Yes | Livedo reticularis | Ischemic stroke | Splenomegaly | No | pos | neg | No | No |
2 | G47A/Y453C | European Caucasian | 1 y | Yes | Livedo reticularis, erythematous and urticarial rash | Ischemic and haemorrhagic strokes | Hepatomegaly, splenomegaly. Portal hypertension. | Pancytopenia, hypoIg | pos | neg | No | No | |
3 | R169Q/deletion | European Caucasian | 1,5 y | Yes | Livedo reticularis, urticarial rash | Ischemic and haemorrhagic strokes | Hepatomegaly, splenomegaly, chronic gastritis | Leucopoenia, hypoIg | neg | neg | No | No | |
4 | G47A/H112Q | European Caucasian | 5 m | Yes | Livedo reticularis, urticarial rash | Ischemic and haemorrhagic strokes | Hepatomegaly, splenomegaly, portal hypertension. | Pancytopenia, HypoIg | neg | neg | No | No | |
5 | R169Q/Y453C | European Caucasian | 1,5 y | Yes | Livedo reticularis | Ischemic stroke | Hepatomegaly, splenomegaly. | Leucopoenia, hypoIg | neg | neg | No | No | |
6 | M1T/I93T | European Caucasian | 1,5 y (died 16 y) | Yes | Non-Langerhans cell histiocytosis | Ischemic stroke | Hepatomegaly, splenomegaly. portal hypertension. | No | neg | neg | Yes | Evans syndrome | |
7 | G47R/G47R | Turkish | 3,5 y | Yes | Livedo reticularis, erythema nodosum | Ischemic stroke III cranial nerve paralysis | No | No | neg | neg | No | No | |
8 | G47R/G47R | Tukish | 4 y | Yes | Livedo reticularis, erythema nodosum | Ischemic stroke | Bowel perforation | No | neg | neg | No | Macrophage activation syndrome | |
9 | G47R/G47R | Turkish | 9 y (died 22 y) | Yes | Livedo reticularis, ulceration of extremities | No | Hepatomegaly, splenomegaly | Leucopoenia | pos | neg | No | Renal amyloidosis, necrotising pneumonia | |
van Montfrans et al. | 1 | R169Q/R169Q | NA | 6 m | No | Livedo reticularis | No | Hepatomegaly, splenomegaly | Granulocytopenia, red-cell aplasia | NA | NA | No | No |
2 | R169Q/R169Q | NA | 6 y | Yes | Livedo reticularis | Stroke | Hepatomegaly, splenomegaly | HypoIg, lymphopenia | NA | NA | No | No | |
Bras et al. | 1 | T119A/G142S | European Caucasian | >10 y | Yes | Livedo reticularis, ulcerations of extremities | Stroke | No | No | NA | NA | No | No |
2 | T119A/G142S | European Caucasian | >10 y | Yes | Livedo reticularis, ulcerations of extremities | Stroke | No | No | NA | NA | No | No | |
3 | T119A/G142S | European Caucasian | >10 y | Yes | Livedo reticularis, ulcerations of extremities | Stroke | No | No | NA | NA | No | No | |
4 | T119A/G142S | European Caucasian | >10 y | Yes | Livedo reticularis, ulcerations of extremities | Stroke | No | No | NA | NA | No | No | |
Van Eyck et al. | 1 | G47R/G47R | NA | 5 y | Yes | No | No | Splenomegaly | Lymphadenopathy, anaemia, thrombocytosis | NA | NA | No | |
Garg et al. | 1 | G47R/R306* | Turkish | 1,5 y (died 5 y) | Yes | Skin rash | Hemorrhagic and ischemic stroke. intraparenchymal haemorrhage | No | No | neg | neg | No | Acute respiratory distress syndrome |
Van Eyck et al. | 1 | R169Q/R169Q | African/ Caucasian | 6 m | No | No | Haemorrhagic stroke | Splenomegaly | Pancytopenia, hypoIg, lymphadenopathy, recurrent viral infections | NA | NA | No | No |
2 | R169Q/R169Q | African/ Caucasian | 5 m | No | No | TIA | Bowel perforation (ulcerative bowel disease, no signs of vasculitis) | Leucopoenia, hypoIg, lymphadenopathy, recurrent viral infections | NA | NA | No | No | |
Belot et al. | 1 | R169Q/P193L | European Caucasian | First year | Yes | Livedo reticularis, ulceration of extremities | TIA, ischemic stroke, sensitive polyneuropathy, intracerebral haemorrhage. | Bowel stenosis | HypoIg | neg | neg | No | Oral aphtae |
2 | G47R/G47R | Asian | 1 m | Yes | Erythema nodosum, vasculitic rash | Intracerebral haemorrhage, Ischemic stroke, Optic neuritis | No | No | NA | NA | Yes | Dactylitis, aneurysm of abdominal vessels | |
Westendorp et al. | 1 | R169Q/R169Q | European Caucasian | 3 y | No | Livedo reticularis, nodules | Ischemic stroke, peripheral neuropathy neurosensorial hearing loss | No | No | NA | NA | No | No |
2 | R169Q/R169Q | European Caucasian | 2 y | No | Livedo reticularis | Ischemic stroke | No | No | NA | NA | No | Autism | |
Gonzales Santiago et al. | 1 | K13del/N328K | European Caucasian | 2 y | Yes | Livedo racemosa | No | No | HypoIg | NA | neg | No | No |
2 | K13del/N328K | European Caucasian | 5 y | No | Nodules, erytema of lower extremities | No | No | HypoIg, recurrent infections | NA | NA | No | No | |
Batu et al. | 1 | G47R/G47R | Turkish | 6,5 y | Yes | Livedo reticularis, | No | Abdominal pain | No | NA | NA | No | No |
2 | G47R/G47R | Turkish | 4 y | Yes | Livedo reticularis, erythema nodosum, necrotic ulcers | Stroke | Abdominal pain, hypertransaminasemia | No | pos | NA | Yes | Glomerulosclerosis | |
3 | G47R/G47R | Turkish | 10 y | Yes | Livedo reticularis | No | Abdominal pain | No | NA | NA | No | No | |
Van Montfrans et al. | 1 | R169Q/R169Q | European Caucasian | 1 y | Yes | Livedo reticularis, erythema nodosum, eczema, Raynaud phenomenon | Ischemic stroke, III cranial nerve paralysis | Abdominal pain, hepatomegaly | Adenopathy, hypoIg, pancytopenia | neg | neg | No | Oral aphtae, arthralgia GH deficiency |
2 | R169Q/R169Q | European Caucasian | Birth | No | Livedo reticularis, eczema | No | Abdominal pain, hepatomegaly, splenomegaly | HypoIg, anaemia | ND | ND | No | Jugular vein thrombosis, GH deficiency | |
3 | R169Q/R169Q | European Caucasian | 6 y | No | Livedo reticularis, ulceration of extremities and trunk | No | Hepatomegaly, splenomegaly | Adenopathy, anaemia | neg | neg | No | No | |
4 | R169Q/R169Q | European Caucasian | 3 y | No | Livedo racemosa, erythema nodosum, Raynaud phenomenon | Ischemic stroke, VI cranial nerve paralysis | Hepatomegaly, splenomegaly | HypoIg, recurrent infections, anaemia | neg | neg | No | No | |
5 | R169Q/R169Q | European Caucasian | 1y | No | Eczema | Ischemic stroke, IV cranial nerve paralysis | Splenomegaly | HypoIg, anaemia, leucopoenia | neg | ND | No | Autism | |
6 | R169Q/R169Q | European Caucasian | 9 m | Yes | Eczema | Ischemic stroke, IV cranial nerve paralysis | Abdominal pain, hepatomegaly, splenomegaly | HypoIg, pancytopenia | pos | pos | Yes | Oral aphtae, arthralgia | |
7 | R169Q/R169Q | European Caucasian | 8 y | Yes | Rash | Ischemic stroke, III cranial nerve paralysis | Abdominal pain, acute liver failure | HypoIg, recurrent infections, anaemia,lymphopenia | neg | neg | No | Oral aphtae, arthralgia | |
8 | R169Q/R169Q | African/Caucasian | 6 m | No | Eczema | Intracranial haemorrhage | Hepatomegaly, splenomegaly | HypoIg, adenopath, thrombocytopenia, leucopoenia | neg | neg | No | No | |
9 | R169Q/R169Q | African/Caucasian | 5 m | No | No | No | Bowel ulcerations, colitis, hepatomegaly, splenomegaly | HypoIg, recurrent infections, adenopathy | neg | neg | No | No | |
Fellmann et al. | 1 | Homozygous 22q11.1 deletion (IL17RA and CECR1) | Asian | Birth (Died 16 y) | No | Ichthyosiform rash, oro-vaginal ulcerations | No | No | Recurrent infection (C. Albicans, S. aureus), neutropenia | neg | neg | No | Chronic systemic inflammation, failure to thrive |
2 | Homozygous 22q11.1 deletion (IL17RA and CECR1) | Asian | 2 y | No | Ichthyosiform rash | No | Splenomegaly | Oro-vaginal candidiasis, Staphylococcal skin infections | neg | neg | No | Retinal vasculitis | |
Schepp et al. | 1 | R169Q/ M243R | NA | 18 y | No | No | No | Splenomegaly | HypoIg, recurrent respiratory infections | NA | NA | No | Arthralgia |
2 | R169Q/M243R | NA | 2 m (Died 17 y) | Yes | Erythema nodosum | Intracranial haemorrhage | Splenomegaly | HypoIg, lymphopenia, recurrent urinary tract and respiratory infections | neg | NA | No | Arthritis Failure to thrive. | |