Background: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. Objectives: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. Sources: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. Implications: In the light of the current imbalance between gammaglobulins’ demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.

Background/Objectives: Biotinidase deficiency (BD) is a treatable autosomal recessive disorder included in many newborn screening (NBS) programs. The importance of early diagnosis and treatment is now well established. However, recent studies are emerging on the possibility of increased enzyme activity with age, an observation that raises questions about the long-term validity of the initial classification of these patients. This study aimed to assess the incidence, genetic and clinical features, and, notably, the longitudinal enzymatic trajectory of BD in a cohort identified by NBS in Emilia-Romagna, Italy, with implications for diagnostic re-evaluation and therapeutic decisions. Methods: A retrospective and prospective analysis was conducted on 64 infants recalled after NBS for suspected BD between 2016 and 2020. Biochemical, molecular, and clinical data were collected, and biotinidase (BTD) activity was monitored longitudinally. Affected individuals were supplemented with biotin and followed clinically for at least 5 years. Results: Thirty-one patients were diagnosed with BD (30 partial, 1 profound; incidence 1:5448). A significant and sustained increase in BTD activity was observed from diagnosis through early childhood (p < 0.001 up to 60 months), particularly among patients carrying the p.Asp444His variant. This enzymatic trend suggests a potential remodulation of biochemical classification over time. Genotype–phenotype concordance was high (92%), and clinical outcomes were favorable across the cohort. Conclusions: This study provides new evidence that BTD activity in patients with BD increases progressively, supporting the concept of age-dependent enzyme recovery. Our results support the need for systematic re-evaluation of diagnosis and treatment, especially at 12 months of age, and particularly in patients with evidence of partial activity deficiency and the p.Asp444His mutation.

The authors would like to make the following correction to their published paper

Testicular tissue cryopreservation is increasingly offered to boys facing gonadotoxic therapies. Yet, its long-term clinical significance depends not only on future fertility-restoration technologies but also on how these patients evolve. This narrative review aims to synthesizes the available follow-up literature on boys who underwent testicular tissue cryopreservation, focusing on procedural safety, testicular growth, pubertal progression, endocrine function, semen outcomes in patients reaching adulthood, and the emerging question of whether cryopreserved tissue may ultimately be needed in all cases. We will compare follow-up strategies across centers, highlight the lack of standardized endpoints, and discuss how survivorship data may refine counseling, re-consent, and future management of cryopreserved tissue. The aim is to provide a clinically oriented overview of what current longitudinal cohorts can already tell us, while identifying the key evidence gaps that still limit harmonized follow-up protocols.

Background: Mucopolysaccharidoses (MPSs) are rare lysosomal storage disorders characterized by multisystem involvement; notably, skeletal abnormalities known as dysostosis multiplex and varying degrees of central nervous system impairment. Accurate radiological evaluation is crucial for accurate diagnosis and effective planning. This study aims to describe the clinical and radiological features of patients with MPS managed at our tertiary care center. Methods: We retrospectively reviewed clinical and radiological data from eight patients with confirmed MPS treated at S. Orsola University Hospital (Bologna, Italy) since 2000. Imaging included conventional radiography, supplemented by MRI and CT. The findings were analyzed by MPS subtype and correlated with clinical evolution and therapeutic interventions. A literature review complemented the analysis. Results: The cohort included one patient with MPS I, two with MPS II, one with MPS III, and four with MPS IV. Common skeletal findings were vertebral deformities, hip dysplasia, and shortening of long bones. Patients with MPS IV showed the most severe bone involvement, including pronounced platyspondyly and odontoid hypoplasia. Follow-up imaging demonstrated progression of bone and CNS pathology despite enzyme replacement therapy (ERT). Conclusions: Our findings underscore the pivotal role of imaging in MPS management. Tailored radiological protocols and multidisciplinary care are crucial for optimizing diagnosis and monitoring disease progression.