In recent years, increasing numbers of patients with primary immune deficiency (PID) are being recognized as also suffering from cardiovascular system (CVS) abnormalities. These CVS defects might be explained by infectious or autoimmune etiologies, as well as by the role of specific genes and the immune system in the development and function of CVS tissues. Here, we provide the first comprehensive review of the clinical, potentially pathogenic mechanisms, and the management of PID, as well as the associated immune and CVS defects. In addition to some well-known associations of PID with CVS abnormalities, such as DiGeorge syndrome and CHARGE anomaly, we describe the cardiac defects associated with Omenn syndrome, calcium channel deficiencies, DNA repair defects, common variable immunodeficiency, Roifman syndrome, various neutrophil/macrophage defects, FADD deficiency, and HOIL1 deficiency. Moreover, we detail the vascular abnormalities recognized in chronic mucocutaneous candidiasis, chronic granulomatous disease, Wiskott–Aldrich syndrome, Schimke immuno-osseus dysplasia, hyper-IgE syndrome, MonoMAC syndrome, and X-linked lymphoproliferative disease. In conclusion, the expanding spectrum of PID requires increased alertness to the possibility of CVS involvement as an important contributor to the diagnosis and management of these patients.

Background: Screening newborns for severe combined immunodeficiency (SCID) aims for early identification and treatment of the affected newborns. Adenosine deaminase (ADA) deficiency, a defect in the purine metabolic pathway, is a major cause of SCID and is characterized by the accumulation of adenosine (Ado) and deoxyadenosine (dAdo) in dried blood spots (DBSs). If left untreated, infants with this disorder are at risk of life-threatening infections. Analysis of T-cell receptor excision circles (TRECs) in DBS samples is the gold-standard screening method. However, TREC analysis is insufficient to determine SCID etiology, and a fraction of ADA–SCID may not be detected. Methods: We used the original DBS screening sample to measure Ado, dAdo, and ADA activity. Erythro-9-(2-hydroxy-3-nonyl) adenine was used as an ADA inhibitor to imitate ADA deficiency, making it possible to create quality control material with pathological enzyme activity and metabolite levels. Quantification was achieved by tandem mass spectrometric analysis with a run time of 2.5 min. Results: The 95th percentile reference intervals (n = 588) of Ado and dAdo were 0.9–3.0 and 0.1–0.4 µmol/L, respectively. The 95th percentile reference interval (n = 200) of ADA activity using ¹³C₁₀, ¹⁵N₅ Ado and ¹⁵N₅ dAdo as substrates were 0.8–1.6 and 0.4–0.7 pmol/DBS, respectively. In confirmed ADA patients (n = 4), Ado and dAdo were significantly elevated, whereas ADA activity was almost absent. Conclusion: These novel methods are applied, in our lab, to samples with low TRECs, with no false negative or false positives encountered to date. The potential of using these methods as a primary screening approach for ADA–SCID is in the process of validation. Statement of novelty: New mass spectrometric methods to simultaneously measure adenosine, deoxyadenosine, guanosine, and deoxguanosine, as well as ADA activity in neonatal DBS samples have been developed. This methodology highlights the metabolic nature of ADA–SCID and complements TREC analysis by providing additional biochemical information.

Introduction: Cartilage–hair hypoplasia (CHH) is a rare skeletal dysplasia that presents with various degrees of immunodeficiency, short stature, and a susceptibility to malignancies. Individuals with CHH can present with severe combined immunodeficiency or combined immunodeficiency and are at risk for severe and unusual infections irrespective of their laboratory findings. In addition, individuals with CHH can present with variable skeletal abnormalities, mainly involving the metaphysis of long bones. CHH is a rare disease and familiarity with the variable features is crucial for diagnosis. Methods: We report the clinical, radiological, and genetic findings for 5 patients with proven diagnoses of CHH. Results: In this study we describe a cohort of patients with CHH and present their clinical findings and progressions. In addition, we present the radiological images and the immunological investigations that were done in these patients. Although all the patients in our cohort had poor cellular immunity, they had a variable clinical course. Three out of 5 patients received a bone marrow transplant (BMT) and 2 out of 5 died at an early age (1 after BMT). Those who had poor humoral function had a worse prognosis compared with those with good humoral function. The skeletal findings were characteristic for CHH. Conclusion: CHH is a disease with a variable presentation. Clinicians should be aware of the characteristic skeletal and immunological findings to identify the disease as early as possible. Statement of novelty: We present novel clinical and radiological findings in patients with variable RMRP gene mutations.

Infants with severe combined immune deficiency (SCID) typically present in the first few months of life with severe, recurrent, opportunistic infections, and without definitive treatment the condition is invariably fatal (Gaspar et al. 2013). Many centres believe that protective isolation is required for treatment of SCID patients once diagnosed, and the isolation protocol varies across institutions. This paper describes the isolation protocol for SCID requiring hematopoietic stem cell transplant (HSCT) that has been utilized at our institution for over the last 25 years. We believe that the profound immunodeficiency in SCID patients warrants a more restrictive treatment to limit the morbidity and mortality associated with HSCT. With this protocol, we have seen a very low infection rate in and have a very good survival rate for our SCID population.