| Objective: To analyze the clinical symptoms,pathological manifestations,and gene mutation findings in children with collagen type IV-related nephropathies,to understand the relationship between clinical manifestations,pathological changes and genotypes,improve the understanding of collagen type IV-related nephropathies and reduce delays in diagnosis and treatment.Methods: Theclinical manifestations,relevant laboratory tests,renal biopsies,and genes of children with type Ⅳ collagen-related gene abnormalities diagnosed from July 2010 to December 2020 were retrospectively analyzed.Results:(1)A total of 98 children with type Ⅳ collagen-related genetic abnormalities were included in this group,with a male-to-female ratio of 1.33:1 and a mean age of onset of 4.71±3.45 years,with prevalence in preschool-aged children.(2)Hematuria(63.27%)was the most common initial symptom of collagen type IV-related nephropathies.63(64.29%)of the children reached proteinuria level at the initial diagnosis,and 21(21.43%)showed renal insufficiency.(3)84 children with renal biopsy results,focal segmental glomerular sclerosis was seen in3 cases(6.25%)and crescent formation in 2 cases(4.17%)under light microscopy;20 cases(46.52%)showed uneven thickness,lamination、laceration,and reticular changes of basement membrane under electron microscopy,7 cases(16.27%)showed diffuse basement membrane thinning;24 cases(53.33%)had a positive reaction in indirect immunofluorescence α3、α5 chains staining.(4)64(65.31%)of the children had a family history of nephropathy,28(28.57%)had relatives with uremia or death due to uremia,and the COL4A5 gene mutation group(40.28%)was more common.(5)11 cases(16.42%)had hearing abnormalities,and the median level of 24-hour urinary protein was higher in the hearing abnormal group(1.01 g/24hr)than the normal hearing group(0.28 g/24hr),the results were statistically significant(U=116.00,P<0.05);9 cases(15.00%)had eye abnormalities,the median level of 24-hour urine protein was higher in the ocular abnormal group(0.69 g/24hr)than in the normal group(0.30 g/24hr),the results were statistically significant(U=121.50,P<0.05).(6)Collagen type IV-related nephropathies was predominantly associated with COL4A5 gene mutations(62.24%),with76 new mutation loci(67.86%)out of 112 mutation loci,and the common mutation types were missense mutations(63.39%),shift mutations(11.61%),and splice mutations(14.29%)in that order.(7)Disease classification was more common in AS(84 cases,85.71%),73.81% of children were diagnosed as XLAS,TBMN(3.06%)was rare,and no cases of FSGS were diagnosed,11.22% of children still could not be classified with a specific disease.(8)The mean age of onset with AS in this group was 4.60±3.25 years,the male to female ratio of 1.21:1.Hematuria was clinically more common(47.62%),hearing and ocular abnormalities were predominant in the COL4A5 group(88.89%,87.50%);83.93% of children with COL4A5 mutations had a positive family history of nephropathy.The COL4A3 mutation group with a median level of 24-hour urine protein as0.33(0.20-1.84)g/24 hr,which was higher in the other gene groups(0.22(0.08-0.37)g/24 hr in the COL4A4 group and 0.30(0.13-0.82)g/24 hr in the COL4A5 group).(9)The median follow-up time was 24.37(6.92-45.85)months,2(2.04%)children progressed to end-stage renal disease during the follow-up time,and 5(5.10%)developed positive urine protein conversion during the follow-up.Conclusion: Collagen type IV-related nephropathies starts at an early age,with hematuria as the first clinical manifestation,most children can reach proteinuria level in the early stage of the disease.The disease classification was mostly in AS,and the mutation of the COL4A5 genotype accounted for the largest proportion.Hearing or ocular abnormalities in children at an early age with AS indicated relatively serious renal damage.The clinical manifestations and renal damage of children with COL4A3 mutations were more severe than other genetic groups in AS.The pathological manifestations of children in the early stage with the disease are often atypical,and the clinical symptoms are often similar to those of other kidney diseases. |
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