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• ETI is safe in most liver transplanted patients with CF. • Close monitoring of liver function and tacrolimus level is warranted. • An improvement in lung function after ETI is found also in liver transplanted patients. Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation. A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports. Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %–38 %). In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients. [ABSTRACT FROM AUTHOR]

Background and Aims: We evaluated the effectiveness and safety of pan‐genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct‐acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)‐infected adolescents (12–18 years), older children (6–11 years), and young children (3–5 years). The purpose of this systematic review and meta‐analysis was to inform the World Health Organization (WHO) guidelines. Methods: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV‐infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS‐I tool. Data were pooled using random‐effects models, and certainty of the evidence was assessed using the GRADE approach. Results: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96–100), 96% (90–100), and 96% (83–100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90–99), 93% (86–98), and 83% (70–93), for SOF/VEL, respectively; and 100% (97–100) and 100% (94–100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). Conclusions: All three pan‐genotypic DAA regimens were highly effective and well‐tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single‐arm non‐randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co‐infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO Record: CRD42020146752. [ABSTRACT FROM AUTHOR]

A retrospective multicentre study conducted in Italy analyzed hospitalization trends for bronchiolitis in infants between October 2019 and March 2023. The study found that bronchiolitis cases, particularly those caused by the respiratory syncytial virus (RSV), experienced a significant reduction during the 2020-2021 winter due to preventive measures implemented during the COVID-19 pandemic. However, subsequent winters saw a notable and sustained increase in bronchiolitis hospitalizations, with the 2022-2023 winter period experiencing a 47% higher rate compared to the pre-pandemic winter of 2019-2020. The changing seasonality of bronchiolitis, including altered patterns of RSV circulation, poses challenges for disease control strategies and immunoprophylaxis measures. Further research is needed to monitor the epidemiology of bronchiolitis and inform public health interventions. [Extracted from the article]

LINKED CONTENT: This article is linked to Indolfi et al and Garrido & Macedo papers. To view these articles, visit https://doi.org/10.1111/apt.16037 and https://doi.org/10.1111/apt.16546 [ABSTRACT FROM AUTHOR]

Erythema nodosum (EN), although relatively uncommon in the pediatric population, is the most frequent type of panniculitis in children. The present study aimed to report all the cases of children admitted to our tertiary pediatric hospital with the diagnosis of EN to evaluate the epidemiology, clinical manifestations, etiology, treatment, and the course of this disease in the pediatric age. This observational study retrospectively considered all children evaluated to the emergency room (ER) of Meyer Children's University Hospital, Florence, Italy, discharged with a diagnosis of EN over a 12-year period (from January 2009 to December 2021). Clinical and laboratory data were recorded using a standardized report form. Sixty-eight patients with EN were included. The etiologic diagnosis of EN was made in 38 children (55.9%): 29 (42.6%) had infection-related EN (in particular EBV and β-hemolytic streptococcus), 6 (8.8%) had Crohn's disease, 1 celiac disease, 1 Sjogren syndrome, and 1 Hodgkin lymphoma. In 30 patients (45%), no definitive diagnosis was reached, and they were defined as having idiopathic EN. Most of the laboratory tests were nonspecific. No statistical differences were found in the demographic and clinical data, and the main diagnostic laboratory parameters between patients with idiopathic EN versus those with secondary EN. Conclusion: Since EN can be isolated or the first manifestation of heterogeneous underlying pathologies, some of which can be severe and life-threatening, it is important to recognize it and carry out all the necessary etiological diagnostic investigations to understand its etiology and start the specific treatment. What is Known: • Erythema nodosum (EN) is the most frequent type of panniculitis in children. • It has been associated with a wide spectrum of disorders, such as different types of infection, malignancies, chronic inflammations, and drugs. What is New: • No statistical differences can be found in clinical features as well as laboratory data, between patients with idiopathic EN versus those with secondary EN. • A broad spectrum of investigations and a proper follow-up should be taken into account in order to prevent a delayed or missed secondary EN diagnosis. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Erythema nodosum in children: a cohort study from a tertiary pediatric hospital in Italy" published in the European Journal of Pediatrics. The correction addresses an error in the affiliations of the authors. The correct affiliations are provided in the correction notice. The original article has been corrected. The publisher, Springer Nature, remains neutral regarding jurisdictional claims and institutional affiliations. The authors of the article are Sarah Abu-Rumeileh, Federica Barbati, Giuseppe Indolfi, and Sandra Trapani. [Extracted from the article]

Background: Respiratory Syncytial Virus (RSV) infection mainly affects newborns, infants and young children aged < 2 years. Since an RSV vaccine is in the European Medicines Agency's waitlist validation, nowadays the prevention only includes passive immunization with monoclonal antibodies (mAb). In the present study we aimed at investigating Italian paediatricians' knowledge, attitudes and behaviours towards RSV and its prevention. Methods: From February to May 2023, an anonymous online questionnaire, with answers based on the Likert scale, was administered to a sample of Italian paediatricians' members of the Italian Society of Paediatrics. Descriptive and inferential statistical analyses were performed using STATA 17. Results: The paediatricians who answered the questionnaire were 507, mostly women (70.6%), aged 30–45 (33.1%), employed in hospitals in 66.6% of cases. The 10.8% of respondents reported that RSV is transmitted only among children younger than 2 years of age and 80.33% of participants that school-age children are not at risk of developing severe forms of RSV disease. The 25% of participants thought that active immunization is currently available to prevent RSV infection and 35.7% that does not exist passive immunization to prevent RSV for infants and newborns aged < 2 years. The 97.5% of physicians managed bronchiolitis cases and 65.6% of participants did not prescribe the administration of mAb. Higher age, seniority and RSV knowledge score were found to be associated with having a higher mAb knowledge score (p < 0.001) and having a higher RSV knowledge was associated with a higher mAb knowledge score (p < 0.001). The logistic regression model found that the odds of a positive attitude towards mAB knowledge score increased by over 3 times (OR 3.23, 95% CI [1.41, 7.40], p = 0.006) for being female and the odds of a positive attitude towards mAB knowledge score increased by almost 10 times (OR 9.73, 95% CI [3.06, 30.89], p < 0.001) for a one-unit increase in RSV knowledge score. Conclusions: Paediatricians' limited knowledge or awareness could represent a barrier to the implementation of preventive strategies against RSV infection. Strategies to improve paediatricians' education on RSV prevention are, therefore, crucial. [ABSTRACT FROM AUTHOR]

Background & Aims: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health‐related quality of life (HRQL) of children with chronic hepatitis C. Methods: In the non‐commercial, non‐randomized, open‐label PANDAA‐PED study, 50 children aged 6–18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN‐27 questionnaires, which included 5 dimensions of HRQL, for child self‐reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child–parent agreement was analysed using the intra‐class correlation coefficient (ICC) and Bland–Altman test. Results: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well‐being based on the children's self‐assessment (from 48.53 to 51.21, p =.03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p =.06) was noticed. After the treatment, the proportion of children self‐assessing their physical well‐being as below normal significantly decreased from 17% to 5% (p =.007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self‐reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland–Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). Conclusions: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well‐being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future. [ABSTRACT FROM AUTHOR]

This study aims to investigate the sensitivity of microscopy, culture and polymerase chain reaction on three gastric aspirates (GAs) in the microbiological confirmation of active pulmonary tuberculosis (TB) and to identify possible changes in sensitivity derived from the collection of a different number of aspirates. Children with clinical and radiological diagnoses of active pulmonary TB who underwent three GAs between March 2007 and June 2019 were retrospectively evaluated. Clinical, radiological, and microbiological data were collected. The sensitivity of microbiological tests on GAs was calculated. Moreover, differences in sensitivity according to age and radiological pattern were investigated. Overall, 156 children with active pulmonary TB were enrolled with a median age of 51.5 (IQR: 25.2–113.2) months. Microbiological investigations on the first GA showed a sensitivity of 34% (95%CI 26.7, 42), the cumulative sensitivity of first and second GAs was 40.4% (95%CI 32.7, 48.5) and of the three GAs was 47.4% (95%CI 39.8, 55.2). The collection of three GAs leads to an overall increase in sensitivity of the first GA by 13.4% (95%CI 2.8, 24.1%; p=0.014). Moreover, the increase in sensitivity was significantly higher in children ≤ 4 years of age and in those with uncomplicated TB (p=0.008). Conclusions: Performing a higher number of GAs increases the sensitivity of microbiological confirmation of active pulmonary TB, particularly in children ≤ 4 years and with an uncomplicated radiological pattern. What is known: • The diagnosis of paediatric tuberculosis is a challenge for paediatricians • Despite their low sensitivity gastric aspirates represent the standard sample for microbiological confirmation of active pulmonary tuberculosis in children • Most international guidelines recommend performing three sequential gastric aspirates on three consecutive days What is new: • A significant increase in global sensitivity by 13.4% was found by the collection of three gastric aspirates compared to the first one • Performing a higher number of gastric aspirates increases the sensitivity of microbiological confirmation, particularly in children ≤ 4 years and with an uncomplicated radiological pattern [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of this non‐commercial, open‐label, real‐life, non‐randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6–18 years with chronic hepatitis C virus (HCV) infection. Methods: Fifty patients qualified for the 12‐week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real‐time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). Results: Median age of the participants was 10 (IQR 8–12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty‐seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty‐three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5–13) versus 9 (IQR 8–11) years (p = 0.008). Conclusions: Results of the PANDAA‐PED study indicated a 100% effectiveness of a 12‐week therapy with SOF/VEL in children aged 6–18 years with chronic HCV infection and its good safety profile, in particular in younger patients. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been variably associated with thromboembolic events (TEs) in children. The aim of our study was to assess the prevalence of TEs in children hospitalized during a five-year period in a tertiary pediatric hospital, particularly in patients with COVID-19 and MIS-C. Overall, 38 patients were discharged with the diagnosis of TE: 20 in the pre-pandemic and 18 in the pandemic period. The prevalence of TEs was the same (0.08%) in the pre-pandemic and pandemic periods. The occurrence of TEs was higher in patients with COVID-19 or MIS-C (6/517, 1.16%) when compared to children without these conditions in the pandemic and in the pre-pandemic periods. The prevalence of TEs in children with MIS-C was significantly higher than the prevalence in patients with COVID-19. Five out of six of the patients with COVID-19 or MIS-C developing a TE had at least one predisposing factor to thrombosis. In conclusion, our study shows an increased prevalence of TEs in children hospitalized with COVID-19 or MIS-C, if compared to children without COVID-19 or MIS-C in the pandemic period and in the pre-pandemic period. The prevalence of TEs was significantly higher in patients with MIS-C. [ABSTRACT FROM AUTHOR]

Background Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%–40% of vertically acquired HCV infections clear spontaneously within 4–5 years. Methods Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA–negative infants in whom RNA was not detectable until after 6 weeks. Results Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1–81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1–18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0–76.9), 39.7% (CrI, 17.9–65.9), and 20.9% (CrI, 4.6–44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. Conclusions Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment. [ABSTRACT FROM AUTHOR]

Background It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%–6% in monoinfected women, and that 25%–40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates "net" of clearance. Methods We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. Results Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%–8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%–16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%–4.1%), and 4.1% (95% CrI, 1.7%–7.3%). We estimated that 24.8% (95% CrI, 12.1%–40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%–83.3%) later in utero, and 9.3% (95% CrI, 0.5%–30.6%) during delivery. Conclusions Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero. [ABSTRACT FROM AUTHOR]

Bartonella henselae is an unusual and rarely suspected osteomyelitis etiologic agent. We present a case of low back‐pain in a 10‐year‐old female which lead to a challenging diagnostic work‐up due to subtle imaging findings. The diagnosis was Bartonella henselae vertebral osteomyelitis mimicking bone tumor. Bartonella infection should be included in the differential diagnosis of pediatric back pain associated with fever, especially if there is a history of exposure to cats. MRI is the most sensitive radiographic technique to define bone lesions, but in case of non‐specific findings, the biopsy of the lesion is mandatory. [ABSTRACT FROM AUTHOR]

Background: Cerebrotendinous xanthomatosis (CTX) is a disorder of bile acid (BA) metabolism due to biallelic mutations in CYP27A1. The deposition of cholesterol and cholestanol in multiple tissues results, manifesting as neurologic disease in adults or older children. Neonatal cholestasis (NC) as a presentation of CTX is rare; it may self‐resolve or persist, evolving to require liver transplantation (LT). Methods: We present in the context of similar reports an instance of CTX manifest as NC and requiring LT. Results: A girl aged 4mo was evaluated for NC with normal serum gamma‐glutamyl transpeptidase activity. An extensive diagnostic work‐up, including liver biopsy, identified no etiology. Rapid progression to end‐stage liver disease required LT aged 5mo. The explanted liver showed hepatocyte loss and micronodular cirrhosis. Bile salt export pump (BSEP), encoded by ABCB11, was not demonstrable immunohistochemically. Both severe ABCB11 disease and NR1H4 disease—NR1H4 encodes farsenoid‐X receptor, necessary for ABCB11 transcription—were considered. However, selected liver disorder panel sequencing and mass‐spectrometry urinary BA profiling identified CTX, with homozygosity for the predictedly pathogenic CYP27A1 variant c.646G > C p.(Ala216Pro). Variation in other genes associated with intrahepatic cholestasis was not detected. Immunohistochemical study of the liver‐biopsy specimen found marked deficiency of CYP27A1 expression; BSEP expression was unremarkable. Aged 2y, the girl is free from neurologic disease. Conclusions: Bile acid synthesis disorders should be routinely included in the NC/"neonatal hepatitis" work‐up. The mutually supportive triple approach of BA profiling, immunohistochemical study, and genetic analysis may optimally address diagnosis in CTX, a treatable disease with widely varying presentation. [ABSTRACT FROM AUTHOR]

The aim of our study was to better define the clinical pattern of diencephalic syndrome, a rare but potentially lethal cause of failure to thrive in infancy. Poor weight gain or weight loss, the characteristic presenting feature, often firstly attributed to gastrointestinal or endocrinological or genetic diseases, is secondary to a malfunctioning hypothalamus, caused by a diencephalic tumor. Due to its unexpected clinical onset, diagnostic delay and misdiagnosis are common. We described a case series of 3 children with diencephalic syndrome admitted at our Hospital, over a 5-year period. Furthermore, a narrative review on all pediatric cases published in the last seventy years was performed. Clinical pattern, timing to diagnosis, neuroimaging, management, and outcome were analyzed. Our three cases are singularly described in all clinical and diagnostic findings. Overall, 100 children were selected; all these cases as well as our children presented with failure to thrive: 96% had body mass index or weight-length/height ratio lower than 5th percentile. Vomiting and hyperactivity are reported in 35 and 26% of cases, respectively. The neurological features, mainly nystagmus reported in 43%, may occur late in the disease course. In conclusion, the diagnostic delay is the hallmark of diencephalic syndrome, confirming the lack of knowledge by clinicians. The poor weight gain/loss despite adequate length growth and food intake, especially in children with hyperactivity and good psychomotor development, should alert pediatricians towards this condition, before neurological signs/symptoms occurrence. [ABSTRACT FROM AUTHOR]

Introduction and objectives: Immunoglobulin A vasculitis (IgAV), the most common childhood vasculitis, is associated with gastrointestinal (GI) involvement in 50–75% of cases. The aim of this study was to describe the characteristics of GI involvement in a cohort of hospitalized children with IgAV. Methods: We retrospectively evaluated patients hospitalized for IgAV at Meyer Children's University Hospital, from January 2010 to December 2020. The children's families were interviewed by phone and asked about disease relapses. Results: In the study period, 118 children had GI involvement, corresponding to 75% of children hospitalized for IgAV. Their median age was 7 years (interquartile range 6–9). The most frequent GI manifestations were abdominal pain (96%), bleeding (71%, mostly occult), vomiting (58%), and diarrhea (17%). GI complications, observed in 18%, were intussusception (14%), appendicitis (3%), gallbladder hydrops (2%), and ileal perforation (1%). Abdomen ultrasound, performed in all cases, was abnormal in 68%. Abdomen X-ray, performed in 19 patients, showed pathologic findings in 84% of them. Selected children with severe manifestations also underwent abdomen computed tomography (2/118; 2%) and GI endoscopy (5/118; 4%). Steroids were used in 80 (67.8%) cases. The use of second- and third-line therapies was necessary in three cases. Relapses, investigated in 80 cases (68%), occurred in 21% of them. Key Points • The present retrospective study describes a cohort of 118 patients hospitalized for gastrointestinal (GI) involvement in immunoglobulin A vasculitis (IgAV) at a tertiary care children's hospital from January 2010 to December 2020. • The most frequent GI manifestations were abdominal pain (96%), vomiting (58%), and diarrhea (17%). GI bleeding was reported in 71% of children, and it was occult in most cases. • GI complications, occurring in 18% of cases, were intussusception (14%), appendicitis (3%), gallbladder hydrops (2%), and ileal perforation (1%). • Steroid treatment has been successfully used in severe GI manifestations; however, our data do not support its association with low relapse risk. Conclusions: The present study describes a large pediatric cohort of GI involvement in IgAV. Steroid treatment should be used when GI manifestations are severe. The association of steroid use with relapse risk is not currently established. [ABSTRACT FROM AUTHOR]

Purpose: Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods: Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results: Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion: In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity. [ABSTRACT FROM AUTHOR]