To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening.

Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.4(ASL):c.283C>T (p.Arg95Cys) and a likely benign variant NM_000048.4(ASL): c.1319T>C (p.Leu440Pro). Functional characterisation of the likely benign genetic variant in ASL was performed. Genomic sequencing was performed on the index patient presenting with non-specific symptoms of poor feeding and lethargy and shown to have increased serum and urine argininosuccinic acid. Functional assay using HEK293T cell model was performed. ASL enzymatic activity was reduced for Leu440Pro. This study highlights the role of functional testing of a variant that may appear benign in a patient with a phenotype consistent with ASL deficiency, and reclassifies NM_000048.4(ASL): c.1319T>C (p.Leu440Pro) variant as likely pathogenic.

Epidemiology and Outcome of Nailbed Injuries Managed in Children's Emergency Department: A 10-Year Single-Center Experience.

BACKGROUND: Fingertip injuries are among the most common hand injuries in children and result in significant health, time, and a financial burden. Nailbed injuries constitute a large proportion of fingertip injuries and are frequent in children. OBJECTIVES: This study aimed to examine the epidemiology, injury patterns, and treatment strategies implemented in patients with nailbed injuries between 0 and 18 years of age. We also wanted to identify various acute and chronic complications associated with nailbed injuries in these patients. METHODS: This was a single-center retrospective study carried out on the data collected between October 1, 2009, and October 31, 2019. RESULTS: We identified 457 patients with upper extremity nailbed injuries during the study period. Most children were male, accounting for 62.8% (287) of the patients. Door crush injuries (59.5%) resulted in the majority of the nailbed injuries. The commonest place of injury occurrence was home (46.4%), followed by playground (28.4%). The next most frequent areas were public areas (17.5%) and school (7.7%). Simple nailbed laceration with partial avulsion of the nail (44.4%) was the most common type of nailbed injury. Most nailbed injury repairs were done by the pediatric emergency doctor (72.2%). The predictors for the occurrence of complications after nailbed injury were the type of injury (stellate laceration and severe crushed nailbed injuries) and fracture of the distal phalanx. The predictors for the use of antibiotics after nailbed injury in our patients were the mechanism of injury (crushed in door, sports injury, and road traffic accident) and fracture of the distal phalanx. Age was found to be associated with subungual hematomas and avulsion, whereas female sex was found to be associated with crush injuries. CONCLUSIONS: In this study, most patients (72.2%) had their nailbed injuries repaired by pediatric emergency doctors. The commonest mechanism of nailbed injury was door crush injuries. Increased awareness and education of the caregivers might help avoid these injuries because the injury mechanism in most of the patients is preventable. Partial nail avulsion with underlying simple laceration of the nailbed was the most frequent type of nailbed injury seen. The complications that were seen after nailbed injuries were fingertip sensitivity (5.3%), split nail deformity (5.3%), infection (3.9%), nonadherence of the nail plate (2%), and hook nail deformity (1%). The predictors for the occurrence of complications after nailbed injury were the type of injury (stellate laceration and severe crushed nailbed injuries) and fracture of the distal phalanx. The predictors for the use of antibiotics after nailbed injury in our patients were the mechanism of injury (crushed in door, sports injury, and road traffic accident) and fracture of the distal phalanx. Age was found to be associated with subungual hematomas and avulsion, whereas female sex was found to be associated with crush injuries. Possessing a robust understanding of the mechanism of injury and the underlying anatomy with a detailed assessment of the nailbed injury is of paramount importance in the management of these patients. An initial thorough assessment and meticulous repair of the nailbed injuries will result in good outcomes with overall few complications.

The Potential Use of Metformin, Dipyridamole, N-Acetylcysteine and Statins as Adjunctive Therapy for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune condition that can potentially affect every single organ during the course of the disease, leading to increased morbidity and mortality, and reduced health-related quality of life. While curative treatment is currently non-existent for SLE, therapeutic agents such as glucocorticoids, mycophenolate, azathioprine, cyclosporine, cyclophosphamide and various biologics are the mainstay of treatment based on their immunomodulatory and immunosuppressive properties. As a result of global immunosuppression, the side-effect profile of the current therapeutic approach is unfavourable, with adverse effects including myelosuppression, infection and malignancies. Hydroxychloroquine, one of the very few Food and Drug Administration (FDA)-approved medications for the treatment of SLE, has been shown to offer a number of therapeutic benefits to SLE patients independent of its immunomodulatory effect. As such, it is worth exploring drugs similar to hydroxychloroquine that confer additional clinical benefits unrelated to immunosuppressive mechanisms. Indeed, apart from hydroxychloroquine, a number of studies have explored the use of a few conventionally non-immunosuppressive drugs that are potentially useful in the management of SLE. In this review, non-immunosuppressive therapeutic agents, namely metformin, dipyridamole, N-acetylcysteine and statins, will be critically discussed with regard to their mechanisms of action and efficacy pertaining to their potential therapeutic role in SLE.