[Genetic analysis of a child with atypical Hemolytic uremic syndrome and nephrotic-range proteinuria].

OBJECTIVE: To explore the clinical characteristics and genetic etiology for a child with atypical Hemolytic uremic syndrome (aHUS) in conjunct with nephrotic level proteinuria. METHODS: A child patient who had visited the Affiliated Hospital of Qingdao University on June 25, 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was carried out for the child, and candidate variant was verified by Sanger sequencing of the child and his parents. RESULTS: The child, an 8-month-old male, had presented mainly with edema, oliguria, hematuria, nephrotic level proteinuria, anemia, thrombocytopenia, increased creatinine and urea, hypercholesterolemia but normal complement levels. Genetic testing revealed that he has harbored compound heterozygous variants of the DGKE gene, namely c.12_18dupGAGGCGG (p.P7fs*37) and c.1042G>T (p.D348Y), which were respectively inherited from his father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variants were classified as likely pathogenic and variant of uncertain significance, respectively. By combining his clinical manifestations and results of genetic testing, the child was diagnosed with aHUS with nephrotic level proteinuria. CONCLUSION: For infants and young children with aHUS in conjunct with nephrotic level proteinuria, variants of the DGKE gene should be screened. Above finding has expanded the mutational spectrum of the DGKE gene.

Efficacy and safety of belimumab for the treatment of refractory childhood-onset systemic lupus erythematosus: A single-center, real-world, retrospective study.

Objective: This study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE). Methods: Twenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data. Results: The mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P 25, P 75: 3, 17); and the mean Physician's Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P<0.05) as well as an elevated complement (C) 3 and C4 levels at 4, 12, 24, and 52 weeks of treatment. In addition, the SLEDAI-2K and PGA scores as well as the percentage of CD19+ B cells were significantly decreased at 12, 24, and 52 weeks of treatment compared with the baseline values (P<0.05). The dosage of glucocorticoid at 4, 12, 24, and 52 weeks of treatment was significantly less than that at baseline or the previous follow-up (P<0.05). At 52 weeks, 14 subjects (53.8%) achieved Lupus Low Disease Activity State (LLDAS), and 4 subjects (15.4%) reached clinical remission (CR). At the last follow-up, 16 subjects (61.5%) achieved LLDAS, and 10 subjects (38.5%) reached CR. Conclusions: Belimumab treatment can significantly improve laboratory indicators, reduce disease activity, and decrease the dosage of glucocorticoid required in children with cSLE. Moreover, it has a good safety profile.

Clinical Features and Familial Mutations in an Autosomal-Inherited Alport Syndrome Patient With the Presentation of Nephrotic Syndrome.

Background: The aim of this study was to report the clinical features and mutations in a patient with autosomal-inherited Alport syndrome (AS). Methods: We examined the clinical data, mutation analysis results, and family tree of a patient with autosomal-inherited AS, who had nephrotic syndrome as her first manifestation. Results: The proband was a girl of 11 months who presented with nephritic and nephrotic syndromes including gross hematuria but had a normal renal function. Her treatment course was complicated by steroid resistance and a poor response to cyclosporine A and cyclophosphamide pulse therapy. Renal biopsy was performed 2 years after disease onset; light microscopy showed glomerular segmental mesangio-proliferative lesions, and type IV collagen staining showed the loss of the α3 chain in the glomerular and tubular basement membrane (GBM and TBM) and α5 chain loss in the GBM. Electron microscopy showed uneven GBM thickness, with the dense basement membrane (BM) layer obviously delaminated and torn, showing a typical "lace-like" change. The segmental BM was loosened and widened. Her father did not develop microscopic hematuria until 10 years later, while her grandmother had asymptomatic hematuria and proteinuria when the proband was diagnosed. We detected a new COL4A4 mutation in the proband, namely c.1715delG (p.G572Vfs * 81) in exon 24. Her father and grandmother carried the same mutation, but her mother and sister did not. Conclusions: We found a new potentially pathogenic mutation of COL4A4 in a patient with autosomal-inherited AS, which presented as nephrotic syndrome in infancy.

Facilitating Anion Transport in Polyolefin-Based Anion Exchange Membranes via Bulky Side Chains.

Highly anion-conductive polymer electrolyte membranes with excellent alkaline stabilities for fuel cell applications were prepared. Thus, a series of polyolefin copolymers with poly(4-methyl-1-pentene) (PMP) moieties containing bulky side chains and side-chain quaternary ammonium (QA) groups were prepared through copolymerization with a Ziegler-Natta catalyst and subsequent quaternization. The separation of hydrophilic microphase and hydrophobic microphase was induced by PMP bulky side chains, and then well-connected ionic domains were formed. This result was confirmed by AFM (atomic force microscopy) and SAXS (small-angle X-ray scattering) analyses. It was discovered that well-defined ionic domains of the PMP-TMA-x (TMA, trimethylamine) membranes depended on the content of PMP moieties. The well-defined ionic domains enhanced the hydroxide conductivity of the PMP-TMA-x membranes despite their lower water uptake (WU) as compared to polypropylene (PP)-containing membranes (PP-TMA-x). The PMP-TMA-41 membrane showed the highest ionic conductivity value (43 mS/cm) while maintaining low WU (29.2 wt %) at room temperature. The membranes mostly preserved (>93.0%) their initial hydroxide conductivity after alkaline treatment (10 M aqueous NaOH, 80 °C, 700 h), thereby revealing desirable alkali stability characteristics. Presumably, the nucleophilic attack from hydroxide or water in the cationic center is inhibited by long alkyl spacers (-CH2-)n (n = 9) which are located between the cation groups and the polymer backbone.