Clinical features of the patients with HA20 haploinsufficiency
| Patient no | Fever | Ulcers | Musculoskeletal | Ocular | Skin | Cardiovascular | Intestinal | Other | Disease-related or treatment-related complications | Other symptoms possibly related to HA20 |
| 1 | With flares | Oral, genital and perineal | Oligoarthritis, then polyarthritis* | Bilateral anterior uveitis | None | None | Bloody diarrhoea | Recurrent URTI and tonsillitis during childhood resulting in tonsillectomy; sometimes LAD (axillary, inguinal) with flares | Severe Cushing syndrome growth retardation, cataract and glaucoma requiring multiple ocular surgeries | Premature ovarian failure, geographic tongue, dental crowding secondary to small jaw |
| 2 | None | Oral, genital and perineal | Polyarthritis with dactylitis* | Bilateral anterior uveitis | None | None | Bloody diarrhoea | Cushing syndrome, cataract and glaucoma requiring multiple ocular surgeries | Acne during adolescence, eczema, pityriasis rosea, geographic tongue, dental crowding secondary to small jaw | |
| 3 | None | Oral and genital* | Polyarthritis | None | Painful pustules in the genital region, breasts, axillae and sacrum, dermal abscess | None | None | Recurrent RTI during childhood | Acne during adolescence, thyroid goitre treated with radiation | |
| 4 | Intermittent | Oral, genital and intestinal | Polyarthritis* | Retinal vasculitis, anterior uveitis | Stevens-Johnson syndrome, malar rash, painful subcutaneous rash, purpura, pustular, folliculitis-like rash on the extremities | None | Diarrhoea, secondary malabsorption syndrome | CNS vasculitis, idiopathic thrombocytopaenic purpura | Steroid-induced diabetes mellitus | |
| 5 | None | Oral and genital* | Polyarthritis | None | Pustular, folliculitis-like rash on the extremities | None | None | Suspicion of pre-eclampsia during pregnancies due to arterial hypertension and proteinuria, later diagnosis of membranous nephropathy | Irregular menses, late menarche (at age 18 years) | |
| 6 | Intermittent | Oral and genital* | Polyarthritis | None | Folliculitis, palmoplantar pustules | None | Diarrhoea, once bloody | Recurrent URTI and tonsillitis during childhood, occasional LAD (neck), intermittent arterial hypertension | Eczema, periodontal disease since childhood, recurrent unintentional weight loss | |
| 7 | With flares | Oral and genital* | Polyarthritis | None | Folliculitis | None | None | Recurrent RTI resulting in tonsillectomy | Removal of fibroids complicated by severe staphylococcus infection | Asthma, enamel loss, uterine fibroids, status postgastric bypass for obesity |
| 8 | With flares | Oral, genital and intestinal | Arthralgia | None | None | Pericardial effusion* | Bloody diarrhoea | Recurrent URTI under azathioprine according to parents | ||
| 9 | Oral and genital* | None | None | None | None | |||||
| 10 | Recurrent* | Oral, rectal and perineal | None | None | None | Pericardial effusion | Abdominal pain, anorexia, nausea, vomiting, weight loss | Recurrent RTI during childhood (starting at 8 weeks of age) resulting in adenoidectomy and tonsillectomy, cervical LAD with fevers | Scoliosis requiring brace and subsequent surgical fusion therapy, vesicoureteral reflux surgery (pyelonephritis), attention deficit hyperactivity disorder | |
| 11 | None | Oral and genital* | None | None | None | None | Abdominal pain, weight loss | Recurrent URTI and otitis media during childhood, requiring repeated tympanostomy, recurrent urinary tract infections | Cerebral palsy due to perinatal lacunar infarction, autism, severe foot pain associated with neurological monoplegia due to cerebral palsy requiring gabapentin and amitriptyline, recurrent headaches | |
| 12 | None | Oral and genital* | Arthralgia | None | Severe acne in adulthood in the face, inguinal region and buttocks | None | Abdominal pain, diarrhoea, rectal bleeding | Recurrent RTI especially during childhood, asthmatic bronchitis | Bilateral pneumonia complicated by empyema, drainage and 3× streptokinase treatment and decortication (right lung) with debridement (pus evacuation), azathioprine-induced severe lymphopaenia and neutropaenia | Dysmenorrhoea resulting in hysterectomy, rosacea |
| 13 | With flares (low-grade) | Oral and genital* | Myalgia | None | Acne-like rash on the extremities | None | None | Hypothyroidism, arthralgia and myalgia (diagnosis of fibromyalgia), ‘Dental problems’ | ||
| 14 | None | Oral and genital* | None | None | None | None | None | |||
| 15 | None | Oral and genital* | None | None | None | None | None | |||
| 16 | With flares* | Oral, intestinal and perineal | None | None | Non-specific rash | Pulmonary embolism | Poor feeding, abdominal pain*, bloody diarrhoea, bowel perforation | Small vessel CNS vasculitis, inflammatory fibroepithelial polyp on the arytenoid | Posterior reversible encephalopathy syndrome, steroid-induced vertebral compression fractures, cataracts, hyperglycaemia and arterial hypertension |
*First symptom/finding leading to medical consultation.
CNS, central nervous system; HA20, A20 haploinsufficiency; LAD, lymphadenopathy; RTI, respiratory tract infection; URTI, upper respiratory tract infection.