Genetic analysis of a child with atypical Hemolytic uremic syndrome and nephrotic-range proteinuria / 中华医学遗传学杂志

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.

Clinical characteristics and gene analysis of a family with autosomal dominant Alport syndrome with the onset of nephrotic syndrome / 中华实用儿科临床杂志

The clinical characteristics, mutation analysis results, and family tree of a patient with autosomal dominant Alport syndrome (ADAS), who had nephrotic syndrome as the first manifestation were examined.The proband was a 11-month-old girl who presented with nephrotic syndromes and gross hematuria.During the treatment course, the patient had steroid resistance and a poor response to Cyclosporine and Cyclophosphamide pulse therapy.Renal biopsy was performed 2 years after disease onset.Under the light microscopy, glomerular segmental mesangio-proliferative lesions were observed.The staining of type Ⅳ collagen showed the loss of the α3 chain in the glomerular basement membrane (GBM) and tubular basement membrane, and α5 chain loss in GBM.Electron microscopy showed uneven thickness of GBM, with obviously delaminated and tearing dense basement membrane (BM) layer, 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.A new mutation in the COL4A4 gene was found in the proband, namely c. 1715delG (p.G572Vfs * 81). Her father and grandmother carried the same mutation, but her mother and sister did not have.The clinical manifestation of ADAS is clinically heterogeneous and its incidence may be higher than what we have expected.

Early catch-up growth status and its influencing factors in small for gestational age preterm infants / 中国新生儿科杂志

Objective To study the early physical growth pattern,catch-up growth situation,and the influencing factors of early growth in small for gestational age (SGA) preterm infants.Method Our study was a single center,retrospective study.Criteria for infant inclusion were prematurity,SGA (birth weight less than the 10th percentile of related gender and gestational week,according to Fenton curve 2013),born between January 2012 to October 2015,admitted to our neonatal intensive care unit (NICU) within 24 h after birth,hospitalization more than 7 days,and discharged with complete oral feeding.Corrected age (CA) was used to evaluate growth.According to our follow up plan,anthropometric data (weight,length,head circumference) were collected at corrected full term (40 ± 4 weeks),CA (3 ± 1.5) months and CA (6 ± 1.5) months.Catch-up growth was defined as ΔZ greater than 0.67 compared with that at birth,successful catch-up was defined as anthropometric data higher than 10th percentile in target population.The characteristics and influencing factors were compared between infants with and without catch-up growth.Result Eighty-one SGA preterm infants were involved,45 boys and 36 girls.The average gestational age was (34.6 ± 1.7) weeks,birthweightwas(1617 ± 348) g,birthlengthwas(41.0 ±3.2)cm and head circumference was (29.7 ± 2.0) cm.At corrected gestational age (40 ± 4) weeks,CA (3 ± 1.5) months and CA (6 ± 1.5) months,follow-up rate was 86.4％,66.7％ and 58.0％;catch-up growth in weight was 32.9％,55.6％ and 66.0％;successful catch-up growth in weight was 52.9％,64.8％ and 66.0％.At CA (40 ±4) weeks,there were more boys,sooner recover birth weight,and less patent ductus arteriosus (PDA) in catch-up infants (P ＜ 0.05).At CA (3 ± 1.5) months,catch-up infants had large gestational age,and they were longer at discharge,shorter hospital stay,less PDA,and greater body weight at CA 40 weeks,the difference was statistically significant (P ＜ 0.05).At CA (6 ± 1.5) months,there were difference in hospitalization days,percentile of body weight at CA 40 weeks and percentile of all three anthropometrics at CA (3 ± 1.5) months between catch-up and no catch-up growth infants (P ＜ 0.05).Multiple factor analysis showed that percentile of weight at CA 3 months was the independent risk factor of catch-up growth in weight at CA 6 months (P =0.002,OR =1.221,95％ CI 1.076 ～ 1.385).For every 5 percentile increase in body weight percentile at CA (3 ± 1.5) months of age,the likelihood of complete body weight catch-up growth at CA (6 ± 1.5) months increased 2.965 times (95％ CI 1.480 ～ 5.942).Conclusion Both weight and length of SGA preterm infants showed a trend of rapid gain between corrected gestational age (40 ± 4) weeks to CA (3 ± 1.5) months.The factors that influencing the completion of catch-up growth are different at different age.The weight,length,and head circumference percentile at CA about 3 months are good predictors of growth pattern and situation at CA 6 months for the SGA preterm infants.