A 7-year-old Caucasian girl, born from non-consanguineous parents, was admitted to the Rheumatology Department of “Bambino Gesú” Children Hospital for a 5 days-history of febrile cough and chronic polyarthritis referred to as present for years. Her physical examination was remarkable for reduction of left basal breath sound and disseminated crackles, as well as for swelling and flexion deformities of both knees and wrists. At admission, complete blood cell count showed neutrophilic leukocytosis and thrombocytosis (white blood cells 40.000/µL, neutrophils 34.000/µL, lymphocytes 3720/µL, platelets 700.000/µL, hemoglobin 11.6 g/dl), with increase in C-reactive protein (180 mg/L). Blood chemistry also showed increase in alanine aminotransferase (ALT 109 U/L) and γ-glutamyl transferase (GGT 203 U/L) levels. Chest X-ray revealed a retrocardiac left basal consolidation, with bronchiectasis images (Fig.
1). A chest CT scan showed a significant pulmonary impairment characterized by a left basal lobe consolidation, bilateral bronchiectasis and interstitial lung disease (ILD) (Fig.
2). The girl was treated with intravenous ceftriaxone with prompt resolution of the respiratory picture. Her past medical history revealed she had experienced at least six other episodes of pneumonia since she was 4-year old, requiring several hospitalization and intravenous antibiotic therapy. Moreover, at the age of 3, she had developed synovitis of both wrists, ankles and knees, which was treated with oral glucocorticoids and with intraarticular injections of glucocorticoids with partial benefit. She also presented with stunted growth (-3 SD for height and weight) and a wobbly gait, consistent with the history of chronic arthritis and joint deformities (see supplementary material). She started walking at 19 months of life and never improved much from her initial wobbly gait. Walking difficulties had been reported by the age of 3, with some falls occurring occasionally. Pediatric sarcoidosis had been previously suspected because of the presence of inflammatory granuloma in the liver biopsy, performed because of persistently increased transaminase levels and mild periportal hyper echogenicity on ultrasound (US). Sarcoidosis was ruled out after detecting normal angiotensin converting enzyme and chitotriosidase blood levels. Based on the coexistence of arthritis and lung involvement, COatomer Protein subunit Alpha (COPA) syndrome was suspected [
2]: however, rheumatoid factor (RF) and interferon signature (IS), were absent or normal, therefore excluding COPA. Taking into account the history of recurrent pneumonia with bronchiectasis, immunological examinations were performed to rule out an immunodeficiency. In addition, tuberculosis, cystic fibrosis and primary ciliary dyskinesia were considered as possible diagnoses and excluded after detecting normal QuantiFERON test, sweat test and bronchial brushing. In contrast, immunologic phenotyping, showed complete IgA and IgE deficiency, together with undetectable levels of antibodies in response to Pneumococcal, Tetanus Toxin and Hemophilus Influenzae B vaccines. Low numbers of B cells, CD4+/CD8 + T cells ratio and recent thymic emigrants (RTE) were found (1.4%), leading to the diagnosis of a combined T and B immunodeficiency (Table
1). Finally, taking into account the presence of the wobbly wide-based gait, previously attributed to chronic arthritis, together with the presence of granuloma in the liver serum alfa-fetoprotein (AFP) levels was measured, which resulted increased (276 ng/ml, normal value < 7 ng/ml). Neurological examination showed normal cranial nerves function, normal tendon reflexes and muscle strength; a subtle telekinetic tremor with a mild dysmetria were noted, so that actually a cerebellar involvement could be suspected (SARA score 7) [
3]. The girl also presented bulbar telangiectasia (Fig.
3) and a diagnosis of A-T was made. This was subsequently confirmed by Whole Exome Sequencing that showed a pathogenic homozygous nonsense variant c.8831_8832del in the ATM gene (p.Leu2945ValfsTer10) [
4]. Despite the lack of consanguinity, the parents came from the same village so that the presence of a genetic isolate could not be excluded. Finally, after pneumonia resolution oxygen supplementation was stopped; an adequate peak expiratory flow was measured, blood gases evaluation was normal and PEP-mask was prescribed at discharge because of the bronchiectasis, along with oral therapy with macrolides and a low daily dose of glucocorticoids [
5].