Neurological symptoms in Schimke immuno-osseous dysplasia in a 11-year-old girl: a case report

Pozadina: Schimkeova imuno-koštana displazija (SIOD, OMIM 242900) rijetka je autosomno recesivna pleiotropna bolest uzrokova- na mutacijama u genu SMARCAL1. SIOD karakterizira trijada simptoma: progresivna bolest bubrega zbog fokalne segmentne glo- meruloskleroze (FSGS), spondiloepifizna displazija i imunodeficijencija T-stanica. Osim toga, tijekom sindroma često se bilježe hete- rogeni neurološki simptomi. Slučaj: Autori opisuju slučaj 14-godišnje djevojčice sa SIOD-om, s ponavljajućim neurološkim simptomima, poput glavobolje nalik migreni, diplopije i napadaja. Rođena je u 34. tjednu trudnoće, s hipotrofijom (1280 g) i niskim rastom (44 cm). Proteinurija nefrot- skog ranga, prvi simptom bolesti, otkrivena je u dobi od 4,5 godine. Štoviše, uočena je značajna imunodeficijencija. Konačno joj je dijagnosticirana Schimkeova imuno-koštana displazija zbog dvije patogene varijante, c.836T>C (p.F279S) i c.2542G>T (p.E848X) identificirane u genu SMARCAL1. Zaključci: Ovo izvješće opisuje klinička obilježja i nalaze neuroslika bolesnika sa SIOD-om. Također prikazuje moguću korelaciju iz- među nastalih neuroloških događaja i Schimkeove bolesti, kako bi se uzela u obzir tijekom dijagnostičkog procesa.Background: Schimke immuno-osseous dysplasia (SIOD, OMIM 242900) is a rare, autosomal recessive, pleiotropic disease caused by mutations in the SMARCAL1 gene. SIOD is characterized by a triad of symptoms, i.e., progressive kidney disease due to focal segmen- tal glomerulosclerosis (FSGS), spondyloepiphyseal dysplasia and T-cell immunodeficiency. Additionally, heterogeneous neurological symptoms are often observed in the course of the syndrome. Case: The authors describe the case of a 14-year-old girl with SIOD, who presented with recurrent neurological symptoms, such as migraine-like headaches, diplopia and seizures. She was born at 34 weeks of pregnancy with hypotrophy (1280 g) and short stature (44 cm). Nephrotic-range proteinuria, the first symptom of the disease, was detected at the age of 4 and a half years. Significant immunodeficiency was also observed. She was finally diagnosed with Schimke immuno-osseous dysplasia on account of two pat- hogenic variants, c.836T>C (p.F279S) and c.2542G>T (p.E848X) identified in the SMARCAL1 gene. Conclusions: This report describes the clinical features and neuroimaging findings of a patient with SIOD. It also presents a possible correlation between neurological events and the Schimke disease, which should be considered during the diagnostic process

Assessment of Interleukin-15 (IL-15) Concentration in Children with Idiopathic Nephrotic Syndrome

Idiopathic nephrotic syndrome (INS) is a chronic glomerular disease in children, characterized by severe proteinuria, hypoalbuminemia, and/or presence of edema and hyperlipidemia. The pathogenesis, however, has not been yet established. The clinical course of the disease is characterized by frequent relapses. Interleukin-15 (IL-15) is a pro-inflammatory cytokine, that apart from its involvement in the immune system, was found to be playing a vital role in various cells’ functioning, including renal tissue. It is desirable to look for new predictors of INS. Our study aimed to evaluate IL-15 as a potential marker in the early diagnosis of the disease. The cohort participating in the study consisted of patients hospitalized in Clinical Hospital No. 1 in Zabrze, from December 2019 to December 2021, including study group with INS (n = 30) and control group (n = 44). Results: The concentration of IL-15 in both serum and urine was significantly elevated in patients with INS, compared to healthy controls. The cytokine might serve as a marker of the disease, however, further research on larger study groups is needed

A Rare De Novo Mutation in the <i>TRIM8</i> Gene in a 17-Year-Old Boy with Steroid-Resistant Nephrotic Syndrome: Case Report

Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. Treatment with steroids is usually successful; however, in a small percentage of patients, steroid resistance is observed. The most frequent histologic kidney feature of steroid-resistant nephrotic syndrome (SRNS) is focal segmental glomerulosclerosis (FSGS). Genetic testing has become a valuable diagnostic tool in defining the etiology of SRNS, leading to the identification of a genetic cause. The TRIM8 gene is expressed in various tissues, including kidney cells and the central nervous system (CNS). An association between a mutation in the TRIM8 gene and an early onset of FSGS has been proposed but is not well described. We present a 17-year-old boy with epilepsy, early mild developmental delay, a low IgG serum level, and proteinuria, secondary to FSGS. A Next-Generation Sequencing (NGS)-based analysis revealed a heterozygous de novo pathogenic variant in the TRIM8 gene (c.1200C>G, p.Tyr400Ter). TRIM8 gene sequencing should be considered in individuals with early onset of FSGS, particularly accompanied by symptoms of cortical dysfunction, such as epilepsy and intellectual disability

Atypical Hemolytic Uremic Syndrome (aHUS) and Adenosine Deaminase (ADA)-Deficient Severe Combined Immunodeficiency (SCID)—Two Diseases That Exacerbate Each Other: Case Report

Hemolytic uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Atypical HUS (aHUS), distinguished by its etiology, is caused by uncontrolled overactivation of the alternative complement pathway. The correct diagnosis of aHUS is complex and involves various gene mutations. Severe combined immunodeficiency (SCID), characterized by severe T-cell lymphocytopenia and a lack of antigen-specific T-cell and B-cell immune responses, is of seldom occurrence. In 10–15% of pediatric patients, SCID is caused by adenosine deaminase (ADA) deficiency. The authors describe the case of a boy who suffered from both aHUS and ADA-deficient SCID. At the age of 9 months, the patient presented acute kidney injury with anuria and coagulopathy. The diagnosis of aHUS was established on the basis of alternative complement pathway deregulation and disease-associated gene mutations. Further examination revealed immune system failure and, at the age of 13 months, the ADA deficiency was confirmed by genetic tests and the boy was diagnosed with ADA-SCID. ADA SCID has recently been described as a possible triggering factor of aHUS development and progression. However, more research is required in this field. Nevertheless, it is crucial in clinical practice to be aware of these two co-existing life-threatening diseases